Intracellular Membrane Fusion

  • Dalu Xu
  • Jesse C. Hay
Part of the Molecular Biology Intelligence Unit book series (MBIU)


Fusion of biological membranes plays an important role in cell structure and function. It is essential for organelle biogenesis, vesicle targeting, constitutive and regulated exocytosis, endocytosis, pathogen invasion of host cells, sperm-egg fusion and skeletal muscle formation. This chapter summarizes our current knowledge of the mechanisms of intracellular membrane fusion with particular emphasis on the structure, function and regulation of the N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein family. The chapter provides details of current ideas on SNARE mechanisms of action in membrane fusion and the conserved features of SNARE complexes. Also covered in detail are SNARE regulation; by lipids, SNARE amino-terminal (NT) domains, posttranslational modifications, SM proteins, tethering proteins, calcium and other regulators. Fusion mechanisms employed by enveloped viruses are also summarized to provide a broader perspective.


Membrane Fusion Fusion Peptide Snare Complex Snare Protein Fusion Pore 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hui SW, Stewart TP, Boni LT et al. Membrane fusion through point defects in bilayers. Science 1981; 212(4497):921–3.PubMedCrossRefGoogle Scholar
  2. 2.
    Siegel DP. Energetics of intermediates in membrane fusion: Comparison of stalk and inverted micellar intermediate mechanisms. Biophys J 1993; 65(5):2124–40.PubMedCrossRefGoogle Scholar
  3. 3.
    Leikin SL, Kozlov MM, Chernomordik LV et al. Membrane fusion: Overcoming of the hydration barrier and local restructuring. J Theor Biol 1987; 129(4):411–25.PubMedCrossRefGoogle Scholar
  4. 4.
    Kozlov MM, Markin VS. Possible mechanism of membrane fusion. Biofizika 1983; 28(2):242–7.PubMedGoogle Scholar
  5. 5.
    Chernomordik L, Kozlov MM, Zimmerberg J. Lipids in biological membrane fusion. J Membr Biol 1995; 146(1):1–14.PubMedGoogle Scholar
  6. 6.
    Siegel DP. The modified stalk mechanism of lamellar/inverted phase transitions and its implications for membrane fusion. Biophys J 1999; 76(1 Pt 1):291–313.PubMedCrossRefGoogle Scholar
  7. 7.
    Kuzmin PI, Zimmerberg J, Chizmadzhev YA et al. A quantitative model for membrane fusion based on low-energy intermediates. Proc Natl Acad Sci USA 2001; 98(13):7235–40.PubMedCrossRefGoogle Scholar
  8. 8.
    Markin VS, Kozlov MM, Borovjagin VL. On the theory of membrane fusion. The stalk mechanism. Gen Physiol Biophys 1984; 3(5):361–77.PubMedGoogle Scholar
  9. 9.
    Kozlovsky Y, Kozlov MM. Stalk model of membrane fusion: Solution of energy crisis. Biophys J 2002; 82(2):882–95.PubMedCrossRefGoogle Scholar
  10. 10.
    Markin VS, Albanesi JP. Membrane fusion: Stalk model revisited. Biophys J 2002; 82(2):693–712.PubMedCrossRefGoogle Scholar
  11. 11.
    Lee J, Lentz BR. Evolution of lipidic structures during model membrane fusion and the relation of this process to cell membrane fusion. Biochemistry 1997; 36(21):6251–9.PubMedCrossRefGoogle Scholar
  12. 12.
    Chernomordik LV, Melikyan GB, Chizmadzhev YA. Biomembrane fusion: A new concept derived from model studies using two interacting planar lipid bilayers. Biochim Biophys Acta 1987; 906(3):309–52.PubMedGoogle Scholar
  13. 13.
    Chanturiya A, Chernomordik LV, Zimmerberg J. Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers. PNAS 1997; 94(26): 14423–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Chernomordik L, Chanturiya A, Green J et al. The hemifusion intermediate and its conversion to complete fusion: Regulation by membrane composition. Biophys J 1995; 69(3):922–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Lentz BR, Lee JK. Poly(ethylene glycol) (PEG)-mediated fusion between pure lipid bilayers: A mechanism in common with viral fusion and secretory vesicle release? Mol Membr Biol 1999; 16(4):279–96.PubMedCrossRefGoogle Scholar
  16. 16.
    Pantazatos DP, MacDonald RC. Direcdy observed membrane fusion between oppositely charged phospholipid bilayers. J Membr Biol 1999; 170(1):27–38.PubMedCrossRefGoogle Scholar
  17. 17.
    Pincet F, Lebeau L, Cribier S. Short-range specific forces are able to induce hemifusion. Eur Biophys J 2001; 30(2):91–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Villar AV, Alonso A, Goni FM. Leaky vesicle fusion induced by phosphatidylinositol-specific phospholipase C: Observation of mixing of vesicular inner monolayers. Biochemistry 2000; 39(46): 14012–8.CrossRefGoogle Scholar
  19. 19.
    Kemble GW, Danieli T, White JM. Lipid-anchored influenza hemagglutinin promotes hemifusion, not complete fusion. Cell 1994; 76(2):383–91.PubMedCrossRefGoogle Scholar
  20. 20.
    Melikyan GB, White JM, Cohen FS. GPI-anchored influenza hemagglutinin induces hemifusion to both red blood cell and planar bilayer membranes. J Cell Biol 1995; 131(3):679–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Bagai S, Lamb RA. Truncation of the COOH-terminal region of the paramyxovirus SV5 fusion protein leads to hemifusion but not complete fusion. J Cell Biol 1996; 135(1):73–84.PubMedCrossRefGoogle Scholar
  22. 22.
    Munoz-Barroso I, Durell S, Sakaguchi K et al. Dilation of the human immunodeficiency virus-1 envelope glycoprotein fusion pore revealed by the inhibitory action of a synthetic peptide from gp41. J Cell Biol 1998; 140(2):315–23.PubMedCrossRefGoogle Scholar
  23. 23.
    Chernomordik LV, Frolov VA, Leikina E et al. The pathway of membrane fusion catalyzed by influenza hemagglutinin: Restriction of lipids, hemifusion, and lipidic fusion pore formation. J Cell Biol 1998; 140(6): 1369–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Qiao H, Armstrong RT, Melikyan GB et al. A specific point mutant at position 1 of the influenza hemagglutinin fusion peptide displays a hemifusion phenotype. Mol Biol Cell 1999; 10(8):2759–69.PubMedGoogle Scholar
  25. 25.
    Razinkov VI, Melikyan GB, Cohen FS. Hemifusion between cells expressing hemagglutinin of influ-enza virus and planar membranes can precede the formation of fusion pores that subsequendy fully enlarge. Biophys J 1999; 77(6):3144–51.PubMedCrossRefGoogle Scholar
  26. 26.
    Armstrong RT, Kushnir AS, White JM. The transmembrane domain of influenza hemagglutinin exhibits a stringent length requirement to support the hemifusion to fusion transition. J Cell Biol 2000; 151(2):425–37.PubMedCrossRefGoogle Scholar
  27. 27.
    Leikina E, Chernomordik LV. Reversible merger of membranes at the early stage of influenza hemagglutinin-mediated fusion. Mol Biol Cell 2000; 11(7):2359–71.PubMedGoogle Scholar
  28. 28.
    Markosyan RM, Cohen FS, Melikyan GB. The lipid-anchored ectodomain of influenza virus hemagglutinin (GPI-HA) is capable of inducing nonenlarging fusion pores. Mol Biol Cell 2000; 11 (4): 1143–52.PubMedGoogle Scholar
  29. 29.
    Melikyan GB, Markosyan RM, Roth MG et al. A point mutation in the transmembrane domain of the hemagglutinin of influenza virus stabilizes a hemifusion intermediate that can transit to fusion. Mol Biol Cell 2000; 11(11):3765–75.Google Scholar
  30. 30.
    Leikina E, LeDuc DL, Macosko JC et al. The 1-127 HA2 construct of influenza virus hemagglutinin induces cell-cell hemifusion. Biochemistry 2001; 40(28):8378–86.PubMedCrossRefGoogle Scholar
  31. 31.
    Kozlov MM, Chernomordik LV. The protein coat in membrane fusion: Lessons from fission. Traffic 2002; 3(4):256–67.PubMedCrossRefGoogle Scholar
  32. 32.
    Breckenridge LJ, Aimers W. Currents through the fusion pore that forms during exocytosis of a secretory vesicle. Nature 1987; 328(6133):814–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Fernandez JM, Neher E, Gomperts BD. Capacitance measurements reveal stepwise fusion events in degranulating mast cells. Nature 1984; 312(5993):453–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Lindau M, Aimers W. Structure and function of fusion pores in exocytosis and ectoplasmic membrane fusion. Curr Opin Cell Biol 1995; 7(4):509–17.PubMedCrossRefGoogle Scholar
  35. 35.
    Aimers W, Tse FW. Transmitter release from synapses: Does a preassembled fusion pore initiate exocytosis? Neuron 1990; 4(6):813–8.CrossRefGoogle Scholar
  36. 36.
    Mayer A. What drives membrane fusion in eukaryotes? Trends Biochem Sci 2001; 26(12):717–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Peters C, Bayer MJ, Buhler S et al. Trans-complex formation by proteolipid channels in the terminal phase of membrane fusion. Nature 2001; 409(6820):581–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Burger KN. Greasing membrane fusion and fission machineries. Traffic 2000; 1(8):605–13.PubMedCrossRefGoogle Scholar
  39. 39.
    Basanez G. Membrane fusion: The process and its energy suppliers. Cell Mol Life Sci 2002; 59(9): 1478–90.PubMedCrossRefGoogle Scholar
  40. 40.
    Basanez G, Goni FM, Alonso A. Effect of single chain lipids on phospholipase C-promoted vesicle fusion. A test for the stalk hypothesis of membrane fusion. Biochemistry 1998; 37(11):3901–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Zimmerberg J, Vogel SS, Chernomordik LV. Mechanisms of membrane fusion. Annu Rev Biophys Biomol Struct 1993; 22:433–66.PubMedCrossRefGoogle Scholar
  42. 42.
    Mayorga LS, Colombo MI, Lennartz M et al. Inhibition of endosome fusion by phospholipase A2 (PLA2) inhibitors points to a role for PLA2 in endocytosis. Proc Natl Acad Sci USA 1993; 90(21):10255–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Nagao T, Kubo T, Fujimoto R et al. Ca(2+)-independent fusion of secretory granules with phospholipase A2-treated plasma membranes in vitro. Biochem J 1995; 307(Pt 2):563–9.PubMedGoogle Scholar
  44. 44.
    Blackwood RA, Transue AT, Harsh DM et al. PLA2 promotes fusion between PMN-specific granules and complex liposomes. J Leukoc Biol 1996; 59(5):663–70.PubMedGoogle Scholar
  45. 45.
    Blackwood RA, Smolen JE, Transue A et al. Phospholipase D activity facilitates Ca2+-induced aggregation and fusion of complex liposomes. Am J Physiol 1997; 272(4 Pt 1):C1279–85.PubMedGoogle Scholar
  46. 46.
    Goni FM, Alonso A. Membrane fusion induced by phospholipase C and sphingomyelinases. Biosci Rep 2000; 20(6):443–63.PubMedCrossRefGoogle Scholar
  47. 47.
    Harsh DM, Blackwood RA. Phospholipase A(2)-mediated fusion of neutrophil-derived membranes is augmented by phosphatidic acid. Biochem Biophys Res Commun 2001; 282(2):480–6.PubMedCrossRefGoogle Scholar
  48. 48.
    Cohen JS, Brown HA. Phospholipases stimulate secretion in RBL mast cells. Biochemistry 2001; 40(22):6589–97.PubMedCrossRefGoogle Scholar
  49. 49.
    Vitale N, Caumont AS, Chasserot-Golaz S et al. Phospholipase Dl: A key factor for the exocytotic machinery in neuroendocrine cells. EMBO J 2001; 20(10):2424–34.PubMedCrossRefGoogle Scholar
  50. 50.
    Humeau Y, Vitale N, Chasserot-Golaz S et al. A role for phospholipase Dl in neurotransmitter release. Proc Natl Acad Sci USA 2001; 98(26): 15300–5.PubMedCrossRefGoogle Scholar
  51. 51.
    Stieglitz KA, Seaton BA, Roberts MF. Binding of proteolytically processed phospholipase D from Streptomyces chromofuscus to phosphatidylcholine membranes facilitates vesicle aggregation and fusion. Biochemistry 2001; 40(46): 13954–63.PubMedCrossRefGoogle Scholar
  52. 52.
    de Figueiredo P, Drecktrah D, Polizotto RS et al. Phospholipase A2 antagonists inhibit constitutive retrograde membrane traffic to the endoplasmic reticulum. Traffic 2000; 1(6):504–11.PubMedCrossRefGoogle Scholar
  53. 53.
    Basanez G, Ruiz-Arguello MB, Alonso A et al. Morphological changes induced by phospholipase C and by sphingomyelinase on large unilamellar vesicles: A cryo-transmission electron microscopy study of liposome fusion. Biophys J 1997; 72(6):2630–7.PubMedCrossRefGoogle Scholar
  54. 54.
    Schmidt A, Wolde M, Thiele C et al. Endophilin I mediates synaptic vesicle formation by transfer of arachidonate to lysophosphatidic acid. Nature 1999; 401(6749): 133–41.PubMedCrossRefGoogle Scholar
  55. 55.
    Weigert R, Silletta MG, Spano S et al. CtBP/BARS induces fission of Golgi membranes by acylating lysophosphatidic acid. Nature 1999; 402(6760):429–33.PubMedCrossRefGoogle Scholar
  56. 56.
    Barr FA, Shorter J. Membrane traffic: Do cones mark sites of fission? Curr Biol 2000; 10(4):R141–144.PubMedCrossRefGoogle Scholar
  57. 57.
    Epand RM, Epand RF. Modulation of membrane curvature by peptides. Biopolymers 2000; 55(5):358–63.PubMedCrossRefGoogle Scholar
  58. 58.
    Hanson PI, Roth R, Morisaki H et al. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 1997; 90(3):523–35.PubMedCrossRefGoogle Scholar
  59. 59.
    Otter-Nilsson M, Hendriks R, Pecheur-Huet EI et al. Cytosolic ATPases, p97 and NSF, are sufficient to mediate rapid membrane fusion. EMBO J 1999; 18(8):2074–83.PubMedCrossRefGoogle Scholar
  60. 60.
    Pollard HB, Caohuy H, Minton AP et al. Synexin (annexin VII) hypothesis for Ca2+/GTP-regulated exocytosis. Adv Pharmacol 1998; 42:81–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Oshry L, Meers P, Mealy T et al. Annexin-mediated membrane fusion in human neutrophils. Trans Assoc Am Physicians 1991; 104:213–20.PubMedGoogle Scholar
  62. 62.
    Chernomordik LV, Leikina E, Kozlov MM et al. Structural intermediates in influenza haemagglutinin-mediated fusion. Mol Membr Biol 1999; 16(1):33–42.PubMedCrossRefGoogle Scholar
  63. 63.
    Graham ME, Burgoyne RD. Comparison of cysteine string protein (Csp) and mutant alpha-SNAP overexpression reveals a role for csp in late steps of membrane fusion in dense-core granule exocytosis in adrenal chromaffin cells. J Neurosci 2000; 20(4):1281–9.PubMedGoogle Scholar
  64. 64.
    Wang CT, Grishanin R, Earles CA et al. Synaptotagmin modulation of fusion pore kinetics in regulated exocytosis of dense-core vesicles. Science 2001; 294(5544): 1111–5.PubMedCrossRefGoogle Scholar
  65. 65.
    Fisher RJ, Pevsner J, Burgoyne RD. Control of fusion pore dynamics during exocytosis by Muncl8. Science 2001; 291(5505):875–8.PubMedCrossRefGoogle Scholar
  66. 66.
    Archer DA, Graham ME, Burgoyne RD. Complexin regulates the closure of the fusion pore during regulated vesicle exocytosis. J Biol Chem 2002; 277(21): 18249–52.PubMedCrossRefGoogle Scholar
  67. 67.
    Eckert DM, Kim PS. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem 2001; 70:777–810.PubMedCrossRefGoogle Scholar
  68. 68.
    Harter C, James P, Bachi T et al. Hydrophobic binding of the ectodomain of influenza hemagglutinin to membranes occurs through the “fusion peptide”. J Biol Chem 1989; 264(11):6459–64.PubMedGoogle Scholar
  69. 69.
    Stegmann T, Delfino JM, Richards FM et al. The HA2 subunit of influenza hemagglutinin inserts into the target membrane prior to fusion. J Biol Chem 1991; 266(27):18404–10.PubMedGoogle Scholar
  70. 70.
    Brunner J, Tsurudome M, eds. Fusion-Protein Membrane Interactions as Studied by Hydrophobic Photolabeling. Boca Raton: CRS Press, 1993.Google Scholar
  71. 71.
    Martin I, Ruysschaert JM. Common properties of fusion peptides from diverse systems. Biosci Rep 2000; 20(6):483–500.PubMedCrossRefGoogle Scholar
  72. 72.
    Wilson IA, Skehel JJ, Wiley DC. Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 A resolution. Nature 1981; 289(5796):366–73.PubMedCrossRefGoogle Scholar
  73. 73.
    Weis WI, Cusack SC, Brown JH et al. The structure of a membrane fusion mutant of the influenza virus haemagglutinin. EMBO J 1990; 9(1):17–24.PubMedGoogle Scholar
  74. 74.
    Bullough PA, Hughson FM, Skehel JJ et al. Structure of influenza haemagglutinin at the pH of membrane fusion. Nature 1994; 371 (6492):37–43.PubMedCrossRefGoogle Scholar
  75. 75.
    Chen J, Skehel JJ, Wiley DC. N-and C-terminal residues combine in the fusion-pH influenza hemagglutinin HA(2) subunit to form an N cap that terminates the triple-stranded coiled coil. Proc Natl Acad Sci USA 1999; 96(16):8967–72.CrossRefGoogle Scholar
  76. 76.
    Skehel JJ, Wiley DC. Receptor binding and membrane fusion in virus entry: The influenza hemagglutinin. Annu Rev Biochem 2000; 69:531–69.PubMedCrossRefGoogle Scholar
  77. 77.
    Weissenhorn W, Dessen A, Harrison SC et al. Atomic structure of the ectodomain from HIV-1 gp41. Nature 1997; 387(6631):426–30.PubMedCrossRefGoogle Scholar
  78. 78.
    Tan K, Liu J, Wang J et al. Atomic structure of a thermostable subdomain of HIV-1 gp41. Proc Natl Acad Sci USA 1997; 94(23): 12303–8.PubMedCrossRefGoogle Scholar
  79. 79.
    Chan DC, Fass D, Berger JM et al. Core structure of gp4l from the HIV envelope glycoprotein. Cell 1997; 89(2):263–73.PubMedCrossRefGoogle Scholar
  80. 80.
    Caffrey M, Cai M, Kaufman J et al. Three-dimensional solution structure of the 44 kDa ectodomain of SIV gp41. EMBO J 1998; 17(16):4572–84.PubMedCrossRefGoogle Scholar
  81. 81.
    Fass D, Harrison SC, Kim PS. Retrovirus envelope domain at 1.7 angstrom resolution. Nat Struct Biol 1996; 3(5):465–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Kobe B, Center RJ, Kemp BE et al. Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins. Proc Nad Acad Sci USA 1999; 96(8):4319–24.CrossRefGoogle Scholar
  83. 83.
    Weissenhorn W, Carfi A, Lee KH et al. Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol Cell 1998; 2(5):605–16.PubMedCrossRefGoogle Scholar
  84. 84.
    Baker KA, Dutch RE, Lamb RA et al. Structural basis for paramyxovirus-mediated membrane fusion. Mol Cell 1999; 3(3):309–19.PubMedCrossRefGoogle Scholar
  85. 85.
    Skehel JJ, Wiley DC. Coiled coils in both intracellular vesicle and viral membrane fusion. Cell 1998; 95(7):871–4.PubMedCrossRefGoogle Scholar
  86. 86.
    Wild CT, Shugars DC, Greenwell TK et al. Peptides corresponding to a predictive alpha-helical domain of human immunodeficiency virus type 1 gp41 are potent inhibitors of virus infection. Proc Natl Acad Sci USA 1994; 91(21):9770–4.PubMedCrossRefGoogle Scholar
  87. 87.
    Wild C, Greenwell T, Matthews T. A synthetic peptide from HIV-1 gp4l is a potent inhibitor of virus-mediated cell-cell fusion. AIDS Res Hum Retroviruses 1993; 9(11):1051–3.PubMedCrossRefGoogle Scholar
  88. 88.
    Wild C, Oas T, McDanal C et al. A synthetic peptide inhibitor of human immunodeficiency virus replication: Correlation between solution structure and viral inhibition. Proc Nad Acad Sci USA 1992; 89(21):10537–41.CrossRefGoogle Scholar
  89. 89.
    Lu M, Blacklow SC, Kim PS. A trimeric structural domain of the HIV-1 transmembrane glycoprotein. Nat Struct Biol 1995; 2(12):1075–82.PubMedCrossRefGoogle Scholar
  90. 90.
    Jiang S, Lin K, Strick N et al. HIV-1 inhibition by a peptide. Nature 1993; 365(6442):113.PubMedCrossRefGoogle Scholar
  91. 91.
    Chen CH, Matthews TJ, McDanal CB et al. A molecular clasp in the human immunodeficiency virus (HIV) type 1 TM protein determines the anti-HIV activity of gp4l derivatives: Implication for viral fusion. J Virol 1995; 69(6):3771–7.PubMedGoogle Scholar
  92. 92.
    Furuta RA, Wild CT, Weng Y et al. Capture of an early fusion-active conformation of HIV-1 gp4l. Nat Struct Biol 1998; 5(4):276–9.PubMedCrossRefGoogle Scholar
  93. 93.
    Tse FW, Iwata A, Aimers W. Membrane flux through the pore formed by a fusogenic viral envelope protein during cell fusion. J Cell Biol 1993; 121(3):543–52.PubMedCrossRefGoogle Scholar
  94. 94.
    Stegmann T, Doms RW, Helenius A. Protein-mediated membrane fusion. Annu Rev Biophys Biophys Chem 1989; 18:187–211.PubMedCrossRefGoogle Scholar
  95. 95.
    Sutton RB, Fasshauer D, Jahn R et al. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature 1998; 395(6700):347–53.PubMedCrossRefGoogle Scholar
  96. 96.
    Poirier MA, Xiao W, Macosko JC et al. The synaptic SNARE complex is a parallel four-stranded helical bundle. Nat Struct Biol 1998; 5(9):765–9.PubMedCrossRefGoogle Scholar
  97. 97.
    McNew JA, Weber T, Parlati F et al. Close is not enough: SNAREdependent membrane fusion requires an active mechanism that transduces force to membrane anchors. J Cell Biol 2000; 150(1):105–17.PubMedCrossRefGoogle Scholar
  98. 98.
    Fasshauer D, Otto H, Eliason WK et al. Structural changes are associated with soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor complex formation. J Biol Chem 1997; 272(44):28036–41.PubMedCrossRefGoogle Scholar
  99. 99.
    Bock JB, Matern HT, Peden AA et al. A genomic perspective on membrane compartment organization. Nature 2001; 409(6822):839–41.PubMedCrossRefGoogle Scholar
  100. 100.
    Lewis MJ, Pelham HR. A new yeast endosomal SNARE related to mammalian syntaxin 8. Traffic 2002; 3(12):922–9.PubMedCrossRefGoogle Scholar
  101. 101.
    Dilcher M, Veith B, Chidambaram S et al. Uselp is a yeast SNARE protein required for retrograde traffic to the ER. EMBO J 2003; 22(14):3664–74.PubMedCrossRefGoogle Scholar
  102. 102.
    Burri L, Varlamov O, Doege CA et al. A SNARE required for retrograde transport to the endoplasmic reticulum. Proc Natl Acad Sci USA 2003; 100(17):9873–7.PubMedCrossRefGoogle Scholar
  103. 103.
    Sollner T, Whiteheart SW, Brunner M et al. SNAP receptors implicated in vesicle targeting and fusion. Nature 1993; 362(6418):318–24.PubMedCrossRefGoogle Scholar
  104. 104.
    Chen YA, Scales SJ, Patel SM et al. SNARE complex formation is triggered by Ca2+ and drives membrane fusion. Cell 1999; 97(2):165–74.PubMedCrossRefGoogle Scholar
  105. 105.
    Fix M, Melia TJ, Jaiswal JK et al. Imaging single membrane fusion events mediated by SNARE proteins. Proc Natl Acad Sci USA 2004; 101(19):7311–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Nickel W, Weber T, McNew JA et al. Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs. Proc Nad Acad Sci USA 1999; 96(22):12571–6.CrossRefGoogle Scholar
  107. 107.
    Hu C, Ahmed M, Melia TJ et al. Fusion of cells by flipped SNAREs. Science 2003; 300(5626):1745–9.PubMedCrossRefGoogle Scholar
  108. 108.
    Coorssen JR, Blank PS, Albertorio F et al. Regulated secretion: SNARE density, vesicle fusion and calcium dependence. J Cell Sci 2003; 116(Pt 10):2087–97.PubMedCrossRefGoogle Scholar
  109. 109.
    Szule JA, Coorssen JR. Revisiting the role of SNAREs in exocytosis and membrane fusion. Biochim Biophys Acta 2003; 1641(2–3):121–35.PubMedGoogle Scholar
  110. 110.
    Duman JG, Singh G, Lee GY et al. Ca(2+) and Mg(2+)/ATP independently trigger homotypic membrane fusion in gastric secretory membranes. Traffic 2002; 3(3):203–17.PubMedCrossRefGoogle Scholar
  111. 111.
    Yang B, Gonzalez Jr L, Prekeris R et al. SNARE interactions are not selective. Implications for membrane fusion specificity. J Biol Chem 1999; 274(9):5649–53.PubMedCrossRefGoogle Scholar
  112. 112.
    Fasshauer D, Antonin W, Margittai M et al. Mixed and noncognate SNARE complexes. Characterization of assembly and biophysical properties. J Biol Chem 1999; 274(22):15440–6.PubMedCrossRefGoogle Scholar
  113. 113.
    McNew JA, Parlati F, Fukuda R et al. Compartmental specificity of cellular membrane fusion encoded in SNARE proteins. Nature 2000; 407(6801):153–9.PubMedCrossRefGoogle Scholar
  114. 114.
    Hua SY, Charlton MP. Activity-dependent changes in partial VAMP complexes during neurotransmitter release. Nat Neurosci 1999; 2(12):1078–83.PubMedCrossRefGoogle Scholar
  115. 115.
    Ungermann C, Sato K, Wickner W. Defining the functions of trans-SNARE pairs. Nature 1998; 396(6711):543–8.PubMedCrossRefGoogle Scholar
  116. 116.
    Bayer MJ, Reese C, Buhler S et al. Vacuole membrane fusion: V0 functions after trans-SNARE pairing and is coupled to the Ca2+-releasing channel. J Cell Biol 2003; 162(2):211–22.PubMedCrossRefGoogle Scholar
  117. 117.
    Fukuda R, McNew JA, Weber T et al. Functional architecture of an intracellular membrane t-SNARE. Nature 2000; 407(6801):198–202.PubMedCrossRefGoogle Scholar
  118. 118.
    Antonin W, Holroyd C, Fasshauer D et al. A SNARE complex mediating fusion of late endosomes defines conserved properties of SNARE structure and function. EMBO J 2000; 19(23):6453–64.PubMedCrossRefGoogle Scholar
  119. 119.
    Antonin W, Fasshauer D, Becker S et al. Crystal structure of the endosomal SNARE complex reveals common structural principles of all SNAREs. Nat Struct Biol 2002; 14:14.Google Scholar
  120. 120.
    Joglekar AP, Xu D, Rigotti DJ et al. The SNARE motif contributes to rbetl intracellular targeting and dynamics independently of SNARE interactions. J Biol Chem 2003; 278(16):14121–33.PubMedCrossRefGoogle Scholar
  121. 121.
    Xu D, Joglekar AP, Williams AL et al. Subunit structure of a mammalian ER/Golgi SNARE complex. J Biol Chem 2000; 275(50):39631–9.PubMedCrossRefGoogle Scholar
  122. 122.
    Fasshauer D, Sutton RB, Brunger AT et al. Conserved structural features of the synaptic fusion complex: SNARE proteins reclassified as Q-and R-SNAREs. Proc Natl Acad Sci USA 1998; 95(26):15781–6.PubMedCrossRefGoogle Scholar
  123. 123.
    Wei S, Xu T, Ashery U et al. Exocytotic mechanism studied by truncated and zero layer mutants of the C-terminus of SNAP-25. EMBO J 2000; 19(6):1279–9.PubMedCrossRefGoogle Scholar
  124. 124.
    Scales SJ, Chen YA, Yoo BY et al. SNAREs contribute to the specificity of membrane fusion. Neuron 2000; 26(2):457–64.PubMedCrossRefGoogle Scholar
  125. 125.
    Katz L, Brennwald P. Testing the 3Q:1R “rule”: Mutational analysis of the ionic “zero” layer in the yeast exocytic SNARE complex reveals no requirement for arginine. Mol Biol Cell 2000; 11(11):3849–58.PubMedGoogle Scholar
  126. 126.
    Ossig R, Schmitt HD, de Groot B et al. Exocytosis requires asymmetry in the central layer of the SNARE complex. EMBO J 2000; 19(22):6000–10.PubMedCrossRefGoogle Scholar
  127. 127.
    Dilcher M, Kohler B, Fischer von Mollard G. Genetic interactions with the yeast Q-SNARE VTI1 reveal novel functions for the R-SNARE YKT6. J Biol Chem 2001; 276(37):34537–44.PubMedCrossRefGoogle Scholar
  128. 128.
    Grote E, Baba M, Ohsumi Y et al. Geranylgeranylated SNAREs are dominant inhibitors of membrane fusion. J Cell Biol 2000; 151(2):453–66.PubMedCrossRefGoogle Scholar
  129. 129.
    Hanson MA, Stevens RC. Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin type B at 2.0 A resolution. Nat Struct Biol 2000; 7(8):687–92.PubMedCrossRefGoogle Scholar
  130. 130.
    Margittai M, Fasshauer D, Pabst S et al. Homo-and heterooligomeric snare complexes studied by site-directed spin labeling. J Biol Chem 2001; 276(16):13169–77.PubMedCrossRefGoogle Scholar
  131. 131.
    Dulubova I, Sugita S, Hill S et al. A conformational switch in syntaxin during exocytosis: Role of muncl8. EMBO J 1999; 18(16):4372–82.PubMedCrossRefGoogle Scholar
  132. 132.
    Fiebig KM, Rice LM, Pollock E et al. Folding intermediates of SNARE complex assembly. Nat Struct Biol 1999; 6(2):117–23.PubMedCrossRefGoogle Scholar
  133. 133.
    Xu T, Rammner B, Margittai M et al. Inhibition of SNARE complex assembly differentially affects kinetic components of exocytosis. Cell 1999; 99(7):713–22.PubMedCrossRefGoogle Scholar
  134. 134.
    Matos MF, Mukherjee K, Chen X et al. Evidence for SNARE zippering during Ca2+-triggered exocytosis in PC12 cells. Neuropharmacology 2003; 45(6):777–86.PubMedCrossRefGoogle Scholar
  135. 135.
    Zhang F, Chen Y, Su Z et al. SNARE assembly and membrane fusion, a kinetic analysis. J Biol Chem 2004; 279(37):38668–72.PubMedCrossRefGoogle Scholar
  136. 136.
    Fasshauer D, Antonin W, Subramaniam V et al. SNARE assembly and disassembly exhibit a pronounced hysteresis. Nat Struct Biol 2002; 14:14.Google Scholar
  137. 137.
    Fasshauer D, Margittai M. A transient interaction of SNAP-25 and syntaxin nucleates SNARE assembly. J Biol Chem 2003.Google Scholar
  138. 138.
    Xiao W, Poirier MA, Bennett MK et al. The neuronal t-SNARE complex is a parallel four-helix bundle. Nat Struct Biol 2001; 8(4):308–311.PubMedCrossRefGoogle Scholar
  139. 139.
    Nicholson KL, Munson M, Miller RB et al. Regulation of SNARE complex assembly by an N-terminal domain of the t-SNARE Ssolp. Nat Struct Biol 1998; 5(9):793–802.PubMedCrossRefGoogle Scholar
  140. 140.
    Rickman C, Meunier FA, Binz T et al. High affinity interaction of syntaxin and SNAP-25 on the plasma membrane is abolished by botulinum toxin E. J Biol Chem 2003.Google Scholar
  141. 141.
    An SJ, Aimers W. Tracking SNARE complex formation in live endocrine cells. Science 2004; 306(5698):1042–6.PubMedCrossRefGoogle Scholar
  142. 142.
    Parlati F, McNew JA, Fukuda R et al. Topological restriction of SNARE-dependent membrane fusion. Nature 2000; 407(6801):194–8.PubMedCrossRefGoogle Scholar
  143. 143.
    Fasshauer D. Structural insights into the SNARE mechanism. Biochim Biophys Acta 2003; 1641(2–3):87–97.PubMedGoogle Scholar
  144. 144.
    Cho SJ, Kelly M, Rognlien KT et al. SNAREs in opposing bilayers interact in a circular array to form conducting pores. Biophys J 2002; 83(5):2522–7.PubMedCrossRefGoogle Scholar
  145. 145.
    Fasshauer D, Eliason WK, Brunger AT et al. Identification of a minimal core of the synaptic SNARE complex sufficient for reversible assembly and disassembly. Biochemistry 1998; 37(29):10354–62.PubMedCrossRefGoogle Scholar
  146. 146.
    Hua Y, Scheller RH. Three SNARE complexes cooperate to mediate membrane fusion. Proc Nad Acad Sci USA 2001; 98(14):8065–70.CrossRefGoogle Scholar
  147. 147.
    Laage R, Rohde J, Brosig B et al. A conserved membrane-spanning amino acid motif drives homomeric and supports heteromeric assembly of presynaptic SNARE proteins. J Biol Chem 2000; 275(23):17481–7.PubMedCrossRefGoogle Scholar
  148. 148.
    Roy R, Laage R, Langosch D. Synaptobrevin transmembrane domain dimerization-revisited. Biochemistry 2004; 43(17):4964–70.PubMedCrossRefGoogle Scholar
  149. 149.
    Kweon DH, Kim CS, Shin YK. Regulation of neuronal SNARE assembly by the membrane. Nat Struct Biol 2003; 10(6):440–7.PubMedCrossRefGoogle Scholar
  150. 150.
    Kweon DH, Kim CS, Shin YK. Insertion of the membrane-proximal region of the neuronal SNARE coiled coil into the membrane. J Biol Chem 2003; 278(14):12367–73.PubMedCrossRefGoogle Scholar
  151. 151.
    Hu K, Carroll J, Fedorovich S et al. Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion. Nature 2002; 415(6872):646–50.PubMedCrossRefGoogle Scholar
  152. 152.
    Hu K, Rickman C, Carroll J et al. A common mechanism for regulation of vesicular SNAREs on phospholipid membranes. Biochem J 2004; 377(Pt 3):781–5.PubMedGoogle Scholar
  153. 153.
    De Haro L, Quetglas S, Iborra C et al. Calmodulin-dependent regulation of a lipid binding domain in the v-SNARE synaptobrevin and its role in vesicular fusion. Biol Cell 2003; 95(7):459–64.PubMedCrossRefGoogle Scholar
  154. 154.
    Quetglas S, Iborra C, Sasakawa N et al. Calmodulin and lipid binding to synaptobrevin regulates calcium-dependent exocytosis. EMBO J 2002; 21(15):3970–9.PubMedCrossRefGoogle Scholar
  155. 155.
    Quetglas S, Leveque C, Miquelis R et al. Ca2+-dependent regulation of synaptic SNARE complex assembly via a calmodulin-and phospholipid-binding domain of synaptobrevin. Proc Nad Acad Sci USA 2000; 97(17):9695–700.CrossRefGoogle Scholar
  156. 156.
    Lang T, Bruns D, Wenzel D et al. SNAREs are concentrated in cholesterol-dependent clusters that define docking and fusion sites for exocytosis. EMBO J 2001; 20(9):2202–13.PubMedCrossRefGoogle Scholar
  157. 157.
    Chamberlain LH, Burgoyne RD, Gould GW. SNARE proteins are highly enriched in lipid rafts in PC 12 cells: Implications for the spatial control of exocytosis. Proc Natl Acad Sci USA 2001; 98(10):5619–24.PubMedCrossRefGoogle Scholar
  158. 158.
    Chamberlain LH, Gould GW. The vesicle-and target-SNARE proteins that mediate Glut4 vesicle fusion are localized in detergent-insoluble lipid rafts present on distinct intracellular membranes. J Biol Chem 2002; 277(51):49750–4.PubMedCrossRefGoogle Scholar
  159. 159.
    Fratti RA, Jun Y, Merz AJ et al. Interdependent assembly of specific regulatory lipids and membrane fusion proteins into the vertex ring domain of docked vacuoles. J Cell Biol 2004; 167(6):1087–98.PubMedCrossRefGoogle Scholar
  160. 160.
    Salaun C, James DJ, Chamberlain LH. Lipid rafts and the regulation of exocytosis. Traffic 2004; 5(4):255–64.PubMedCrossRefGoogle Scholar
  161. 161.
    Knecht V, Grubmuller H. Mechanical coupling via the membrane fusion SNARE protein syntaxin 1A: A molecular dynamics study. Biophys J 2003; 84(3):1527–47.PubMedCrossRefGoogle Scholar
  162. 162.
    Fernandez I, Ubach J, Dulubova I et al. Three-dimensional structure of an evolutionarily conserved N-terminal domain of syntaxin 1A. Cell 1998; 94(6):841–9.PubMedCrossRefGoogle Scholar
  163. 163.
    Munson M, Chen X, Cocina AE et al. Interactions within the yeast t-SNARE Ssolp that control SNARE complex assembly. Nat Struct Biol 2000; 7(10):894–902.PubMedCrossRefGoogle Scholar
  164. 164.
    Munson M, Hughson FM. Conformational regulation of SNARE assembly and disassembly in vivo. J Biol Chem 2002; 277(11):9375–81.PubMedCrossRefGoogle Scholar
  165. 165.
    Parlati F, Weber T, McNew JA et al. Rapid and efficient fusion of phospholipid vesicles by the alpha-Helical core of a SNARE complex in the absence of an N-terminal regulatory domain. Proc Natl Acad Sci USA 1999; 96(22):12565–70.PubMedCrossRefGoogle Scholar
  166. 166.
    Williams AL, Ehm S, Jacobson NC et al. rslyl binding to syntaxin 5 is required for endoplasmic reticulum-to-Golgi transport but does not promote SNARE motif accessibility. Mol Biol Cell 2004; 15(1):162–75.PubMedCrossRefGoogle Scholar
  167. 167.
    Antonin W, Dulubova I, Arac D et al. The N-terminal domains of syntaxin 7 and vtilb form three-helix bundles that differ in their ability to regulate SNARE complex assembly. J Biol Chem 2002; 277(39):36449–56.PubMedCrossRefGoogle Scholar
  168. 168.
    Dulubova I, Yamaguchi T, Gao Y et al. How Tlg2p/syntaxin 16’ snares’ Vps45. EMBO J 2002; 21(14):3620–31.PubMedCrossRefGoogle Scholar
  169. 169.
    Dulubova I, Yamaguchi T, Wang Y et al. Vam3p structure reveals conserved and divergent properties of syntaxins. Nat Struct Biol 2001; 8(3):258–64.CrossRefGoogle Scholar
  170. 170.
    Misura KM, Bock JB, Gonzalez Jr LC et al. Three-dimensional structure of the amino-terminal domain of syntaxin 6, a SNAP-25 C homolog. Proc Natl Acad Sci USA 2002; 99(l4):9184–9.PubMedCrossRefGoogle Scholar
  171. 171.
    Gonzalez Jr LC, Weis WI, Scheller RH. A novel SNARE N-terminal domain revealed by the crystal structure of Sec22b. J Biol Chem 2001; 17:17.Google Scholar
  172. 172.
    Tochio H, Tsui MM, Banfield DK et al. An autoinhibitory mechanism for nonsyntaxin SNARE proteins revealed by the structure of Ykt6p. Science 2001; 293:698–702.PubMedCrossRefGoogle Scholar
  173. 173.
    Gedeon AK, Colley A, Jamieson R et al. Identification of the gene (SEDL) causing X-linked spondyloepiphyseal dysplasia tarda. Nat Genet 1999; 22(4):400–4.PubMedCrossRefGoogle Scholar
  174. 174.
    Jang SB, Kim YG, Cho YS et al. Crystal structure of SEDL and its implications for a genetic disease spondyloepiphyseal dysplasia tarda. J Biol Chem 2002; 277(51):49863–9.PubMedCrossRefGoogle Scholar
  175. 175.
    Lunin VV, Munger C, Wagner J et al. The structure of the MAPK scaffold, MP1, bound to its partner, pi4._A complex with a critical role in endosomal map kinase signaling. J Biol Chem 2004; 279(22):23422–30.PubMedCrossRefGoogle Scholar
  176. 176.
    Hay JC, Hiding H, Scheller RH. Mammalian vesicle trafficking proteins of the endoplasmic reticulum and Golgi apparatus. J Biol Chem 1996; 271(10):5671–9.PubMedCrossRefGoogle Scholar
  177. 177.
    Tang BL, Low DY, Hong W. Hsec22c: A homolog of yeast Sec22p and mammalian rsec22a and msec22b/ERS-24. Biochem Biophys Res Commun 1998; 243(3):885–91.PubMedCrossRefGoogle Scholar
  178. 178.
    Hasegawa H, Zinsser S, Rhee Y et al. Mammalian Ykt6 is a neuronal SNARE targeted to a specialized compartment by its profilin-like amino terminal domain. Mol Biol Cell 2003; l4(2):698–720.CrossRefGoogle Scholar
  179. 179.
    Martinez-Area S, Rudge R, Vacca M et al. A dual mechanism controlling the localization and function of exocytic v-SNAREs. Proc Natl Acad Sci USA 2003; 100(15):9011–6.CrossRefGoogle Scholar
  180. 180.
    Martinez-Area S, Alberts P, Zahraoui A et al. Role of tetanus neurotoxin insensitive vesicle-associated membrane protein (TI-VAMP) in vesicular transport mediating neurite outgrowth. J Cell Biol 2000; l49(4):889–900.CrossRefGoogle Scholar
  181. 181.
    Pryor PR, Mullock BM, Bright NA et al. Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO Rep 2004; 5(6):590–5.PubMedCrossRefGoogle Scholar
  182. 182.
    Hasegawa H, Yang Z, Oltedal L et al. Intramolecular protein-protein and protein-lipid interactions control the conformation and subcellular targeting of neuronal Ykt6. J Cell Sci 2004; 117(Pt 19):4495–508.PubMedCrossRefGoogle Scholar
  183. 183.
    Fukasawa M, Varlamov O, Eng WS et al. Localization and activity of the SNARE Ykt6 determined by its regulatory domain and palmitoylation. Proc Nad Acad Sci USA 2004; 101(14):4815–20.CrossRefGoogle Scholar
  184. L84.
    Dietrich EP, Gurezka R, Veit M et al. The SNARE Ykt6 mediates protein palmitoylation during an early stage of homotypic vacuole fusion. EMBO J 2004; 23(l):45–53.PubMedCrossRefGoogle Scholar
  185. 185.
    Hui N, Nakamura N, Sonnichsen B et al. An isoform of the Golgi t-SNARE, syntaxin 5, with an endoplasmic reticulum retrieval signal. Mol Biol Cell 1997; 8(9):1777–87.PubMedGoogle Scholar
  186. 186.
    Cheever ML, Sato TK, de Beer T et al. Phox domain interaction with PtdIns (3)P targets the Vam7 t-SNARE to vacuole membranes. Nat Cell Biol 2001; 3(7):613–8.PubMedCrossRefGoogle Scholar
  187. 187.
    Neiman AM, Katz L, Brennwald PJ. Identification of domains required for developmentally regulated SNARE function in Saccharomyces cerevisiae. Genetics 2000; 155(4):1643–55.PubMedGoogle Scholar
  188. 188.
    Nakanishi H, de los Santos P, Neiman AM. Positive and negative regulation of a SNARE protein by control of intracellular localization. Mol Biol Cell 2004; 15(4):1802–15.PubMedCrossRefGoogle Scholar
  189. 189.
    Gallwitz D, Jahn R. The riddle of the Secl/Munc-18 proteins — New twists added to their interactions with SNAREs. Trends Biochem Sci 2003; 28(3):113–6.PubMedCrossRefGoogle Scholar
  190. 190.
    Toonen RF, Verhage M. Vesicle trafficking: Pleasure and pain from SM genes. Trends Cell Biol 2003; 13(4):177–86.PubMedCrossRefGoogle Scholar
  191. 191.
    Pevsner J, Hsu SC, Braun JE et al. Specificity and regulation of a synaptic vesicle docking complex. Neuron 1994; 13(2):353–61.PubMedCrossRefGoogle Scholar
  192. 192.
    Bryant NJ, James DE. Vps45p stabilizes the syntaxin homologue Tlg2p and positively regulates SNARE complex formation. EMBO J 2001; 20(13):3380–8.PubMedCrossRefGoogle Scholar
  193. 193.
    Sato TK, Rehling P, Peterson MR et al. Class C Vps protein complex regulates vacuolar SNARE pairing and is required for vesicle docking/fusion. Mol Cell 2000; 6(3):66l–71.CrossRefGoogle Scholar
  194. 194.
    Kosodo Y, Noda Y, Adachi H et al. Binding of Slyl to Sed5 enhances formation of the yeast early Golgi SNARE complex. J Cell Sci 2002; 115(Pt 18):3683–91.PubMedCrossRefGoogle Scholar
  195. 195.
    Misura KM, Scheller RH, Weis WI. Three-dimensional structure of the neuronal-Secl-syntaxin la complex. Nature 2000; 404(6776):355–62.PubMedCrossRefGoogle Scholar
  196. 196.
    Yang B, Steegmaier M, Gonzalez Jr LC et al. Nsecl binds a closed conformation of syntaxin 1 A. J Cell Biol 2000; l48(2):247–52.CrossRefGoogle Scholar
  197. 197.
    Scott BL, Van Komen JS, Irshad H et al. Seclp directly stimulates SNAREmediated membrane fusion in vitro. J Cell Biol 2004; 167(l):75–85.PubMedCrossRefGoogle Scholar
  198. 198.
    Carr CM, Grote E, Munson M et al. Seclp binds to SNARE complexes and concentrates at sites of secretion. J Cell Biol 1999; 146(2):333–44.PubMedCrossRefGoogle Scholar
  199. 199.
    Bracher A, Weissenhorn W. Structural basis for the Golgi membrane recruitment of Slylp by Sed5p. EMBO J 2002; 21(22):6114–24.PubMedCrossRefGoogle Scholar
  200. 200.
    Yamaguchi T, Dulubova I, Min SW et al. Slyl binds to Golgi and ER syntaxins via a conserved N-terminal peptide motif. Dev Cell 2002; 2(3):295–305.PubMedCrossRefGoogle Scholar
  201. 201.
    Peng R, Gallwitz D. Multiple SNARE interactions of an SM protein: Sed5p/Slylp binding is dispensable for transport. EMBO J 2004; 23(20):3939–49.PubMedCrossRefGoogle Scholar
  202. 202.
    Graham ME, Barclay JW, Burgoyne RD. Syntaxin/Muncl8 interactions in the late events during vesicle fusion and release in exocytosis. J Biol Chem 2004; 279(31):32751–60.PubMedCrossRefGoogle Scholar
  203. 203.
    Arac D, Dulubova I, Pei J et al. Three-dimensional structure of the rSlyl N-terminal domain reveals a conformational change induced by binding to syntaxin 5. J Mol Biol 2005; 346(2):589–601.PubMedCrossRefGoogle Scholar
  204. 204.
    Bryant NJ, James DE. The Seclp/Muncl8 (SM) protein, Vps45p, cycles on and off membranes during vesicle transport. J Cell Biol 2003; l61(4):691–6.CrossRefGoogle Scholar
  205. 205.
    Peng R, Gallwitz D. Slyl protein bound to Golgi syntaxin Sed5p allows assembly and contributes to specificity of SNARE fusion complexes. J Cell Biol 2002; 157(4):645–55.PubMedCrossRefGoogle Scholar
  206. 206.
    Gissen P, Johnson CA, Morgan NV et al. Mutations in VPS33B, encoding a regulator of SNAREdependent membrane fusion, cause arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome. Nat Genet 2004; 36(4):400–4.PubMedCrossRefGoogle Scholar
  207. 207.
    Zerial M, McBride H. Rab proteins as membrane organizers. Nat Rev Mol Cell Biol 2001; 2(2):107–17.PubMedCrossRefGoogle Scholar
  208. 208.
    Whyte JR, Munro S. Vesicle tethering complexes in membrane traffic. J Cell Sci 2002; 115(Pt 13):2627–37.PubMedGoogle Scholar
  209. 209.
    Sapperstein SK, Lupashin W, Schmitt HD et al. Assembly of the ER to Golgi SNARE complex requires Usolp. J Cell Biol 1996; 132(5):755–67.PubMedCrossRefGoogle Scholar
  210. 210.
    Cao X, Ballew N, Barlowe C. Initial docking of ER-derived vesicles requires Usolp and Yptlp but is independent of SNARE proteins. EMBO J 1998; 17(8):2156–65.PubMedCrossRefGoogle Scholar
  211. 211.
    Broadie K, Prokop A, Bellen HJ et al. Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. Neuron 1995; 15(3):663–73.PubMedCrossRefGoogle Scholar
  212. 212.
    Christoforidis S, McBride HM, Burgoyne RD et al. The Rab5 effector EEA1 is a core component of endosome docking. Nature 1999; 397(6720):621–5.PubMedCrossRefGoogle Scholar
  213. 213.
    Allan BB, Moyer BD, Balch WE. Rabl recruitment of pi 15 into a cis-SNARE complex: Programming budding COPII vesicles for fusion. Science 2000; 289(5478):444–8.PubMedCrossRefGoogle Scholar
  214. 214.
    Shorter J, Beard MB, Seemann J et al. Sequential tethering of Golgins and catalysis of SNAREpin assembly by the vesicle-tethering protein pi 15. J Cell Biol 2002; 157(l):45–62.PubMedCrossRefGoogle Scholar
  215. 215.
    Suvorova ES, Duden R, Lupashin W. The Sec34/Sec35p complex, a Yptlp effector required for retrograde intra-Golgi trafficking, interacts with Golgi SNAREs and COPI vesicle coat proteins. J Cell Biol 2002; 157(4):631–43.PubMedCrossRefGoogle Scholar
  216. 216.
    McBride HM, Rybin V, Murphy C et al. Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. Cell 1999; 98(3):377–86.PubMedCrossRefGoogle Scholar
  217. 217.
    Siniossoglou S, Pelham HR. Vps51p links the VFT complex to the SNARE Tlglp. J Biol Chem 2002; 277(50):48318–24.PubMedCrossRefGoogle Scholar
  218. 218.
    Conibear E, Cleck JN, Stevens TH. Vps51p mediates the association of the GARP (Vps52/53/54) complex with the late Golgi t-SNARE Tlglp. Mol Biol Cell 2003; 14(4):1610–23.PubMedCrossRefGoogle Scholar
  219. 219.
    Laage R, Ungermann C. The N-terminal domain of the t-SNARE Vam3p coordinates priming and docking in yeast vacuole fusion. Mol Biol Cell 2001; 12(ll):3375–85.PubMedGoogle Scholar
  220. 220.
    Fujita Y, Shirataki H, Sakisaka T et al. Tomosyn: A syntaxin-1-binding protein that forms a novel complex in the neurotransmitter release process. Neuron 1998; 20(5):905–15.PubMedCrossRefGoogle Scholar
  221. 221.
    Scales SJ, Hesser BA, Masuda ES et al. Amisyn, a novel syntaxin-binding protein that may regulate SNARE complex assembly. J Biol Chem 2002; 277(31):28271–9.PubMedCrossRefGoogle Scholar
  222. 222.
    Hatsuzawa K, Lang T, Fasshauer D et al. The R-SNARE motif of tomosyn forms SNARE core complexes with syntaxin 1 and SNAP-25 and down-regulates exocytosis. J Biol Chem 2003; 278(33):31159–66.PubMedCrossRefGoogle Scholar
  223. 223.
    Pobbati AV, Razeto A, Boddener M et al. Structural basis for the inhibitory role of tomosyn in exocytosis. J Biol Chem 2004; 279(45):47192–200.PubMedCrossRefGoogle Scholar
  224. 224.
    Sakisaka T, Baba T, Tanaka S et al. Regulation of SNAREs by tomosyn and ROCK: Implication in extension and retraction of neurites. J Cell Biol 2004; 166(1):17–25.PubMedCrossRefGoogle Scholar
  225. 225.
    Lehman K, Rossi G, Adamo JE et al. Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9. J Cell Biol 1999; l46(l):125–40.Google Scholar
  226. 226.
    Sun W, Yan Q, Vida TA et al. Hrs regulates early endosome fusion by inhibiting formation of an endosomal SNARE complex. J Cell Biol 2003; 162(l):125–37.PubMedCrossRefGoogle Scholar
  227. 227.
    Yan Q, Sun W, McNew JA et al. Ca2+ and N-ethylmaleimide-sensitive factor differentially regulate disassembly of SNARE complexes on early endosomes. J Biol Chem 2004; 279(18):18270–6.PubMedCrossRefGoogle Scholar
  228. 228.
    Martin TF. Prime movers of synaptic vesicle exocytosis. Neuron 2002; 34(1):9–12.PubMedCrossRefGoogle Scholar
  229. 229.
    Betz A, Okamoto M, Benseler F et al. Direct interaction of the rat unc-13 homologue Muncl3-1 with the N terminus of syntaxin. J Biol Chem 1997; 272(4):2520–6.PubMedCrossRefGoogle Scholar
  230. 230.
    Sassa T, Harada S, Ogawa H et al. Regulation of the UNC-18-Caenorhabditis elegans syntaxin complex by UNC-13. J Neurosci 1999; 19(12):4772–7.PubMedGoogle Scholar
  231. 231.
    Richmond JE, Weimer RM, Jorgensen EM. An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming. Nature 2001; 412(6844):338–41.PubMedCrossRefGoogle Scholar
  232. 232.
    McMahon HT, Missler M, Li C et al. Complexins: Cytosolic proteins that regulate SNAP receptor function. Cell 1995; 83(1):111–9.PubMedCrossRefGoogle Scholar
  233. 233.
    Reim K, Mansour M, Varoqueaux F et al. Complexins regulate a late step in Ca2+-dependent neurotransmitter release. Cell 2001; 104(1):71–81.PubMedCrossRefGoogle Scholar
  234. 234.
    Tokumaru H, Umayahara K, Pellegrini LL et al. SNARE complex oligomerization by synaphin/ complexin is essential for synaptic vesicle exocytosis. Cell 2001; 104(3):421–32.PubMedCrossRefGoogle Scholar
  235. 235.
    Chen X, Tomchick DR, Kovrigin E et al. Three-dimensional structure of the complexin/SNARE complex. Neuron 2002; 33(3):397–409.PubMedCrossRefGoogle Scholar
  236. 236.
    Bracher A, Kadlec J, Betz H et al. X-ray structure of a neuronal complexin-SNARE complex from squid. J Biol Chem 2002; 277(29):26517–23.PubMedCrossRefGoogle Scholar
  237. 237.
    Pabst S, Margittai M, Vainius D et al. Rapid and selective binding to the synaptic SNARE complex suggests a modulatory role of complexins in neuroexocytosis. J Biol Chem 2002; 277(10):7838–48.PubMedCrossRefGoogle Scholar
  238. 238.
    Hu K, Carroll J, Rickman C et al. Action of complexin on SNARE complex. J Biol Chem 2002; 277(44):4l652–6.CrossRefGoogle Scholar
  239. 239.
    Rein U, Andag U, Duden R et al. ARF-GAP-mediated interaction between the ER-Golgi v-SNAREs and the COPI coat. J Cell Biol 2002; 157(3):395–404.PubMedCrossRefGoogle Scholar
  240. 240.
    Springer S, Schekman R. Nucleation of COPII vesicular coat complex by endoplasmic reticulum to Golgi vesicle SNAREs. Science 1998; 281(5377):698–700.PubMedCrossRefGoogle Scholar
  241. 241.
    Legesse-Miller A, Sagiv Y, Glozman R et al. Aut7p, a soluble autophagic factor, participates in multiple membrane trafficking processes. J Biol Chem 2000; 275(42):32966–73.PubMedCrossRefGoogle Scholar
  242. 242.
    Sagiv Y, Legesse-Miller A, Porat A et al. GATE-16, a membrane transport modulator, interacts with NSF and the Golgi v-SNARE GOS-28. EMBO J 2000; 19(7):1494–504.PubMedCrossRefGoogle Scholar
  243. 243.
    Muller JM, Shorter J, Newman R et al. Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion. J Cell Biol 2002; 157(7):1161–73.PubMedCrossRefGoogle Scholar
  244. 244.
    Peters C, Baars TL, Buhler S et al. Mutual control of membrane fission and fusion proteins. Cell 2004; 119(5):667–78.PubMedCrossRefGoogle Scholar
  245. 245.
    Marash M, Gerst JE. t-SNARE dephosphorylation promotes SNARE assembly and exocytosis in yeast. EMBO J 2001; 20(3):4l1–21.CrossRefGoogle Scholar
  246. 246.
    Marash M, Gerst JE. Phosphorylation of the autoinhibitory domain of the Sso t-SNAREs promotes binding of the Vsml SNARE regulator in yeast. Mol Biol Cell 2003; 14(8):3114–25.PubMedCrossRefGoogle Scholar
  247. 247.
    Gurunathan S, Marash M, Weinberger A et al. t-SNARE phosphorylation regulates endocytosis in yeast. Mol Biol Cell 2002; 13(5):1594–607.PubMedCrossRefGoogle Scholar
  248. 248.
    Hiding H, Scheller RH. Phosphorylation of synaptic vesicle proteins: Modulation of the alpha SNAP interaction with the core complex. Proc Natl Acad Sci USA 1996; 93(21):11945–9.CrossRefGoogle Scholar
  249. 249.
    Nielander HB, Onofri F, Valtorta F et al. Phosphorylation of VAMP/synaptobrevin in synaptic vesicles by endogenous protein kinases. J Neurochem 1995; 65(4):1712–20.PubMedGoogle Scholar
  250. 250.
    Shimazaki Y, Nishiki T, Omori A et al. Phosphorylation of 25-kDa synaptosome-associated protein. Possible involvement in protein kinase C-mediated regulation of neurotransmitter release. J Biol Chem 1996; 271(24):l4548–53.Google Scholar
  251. 251.
    Risinger C, Bennett MK. Differential phosphorylation of syntaxin and synaptosome-associated protein of 25 kDa (SNAP-25) isoforms. J Neurochem 1999; 72(2):6l4–24.CrossRefGoogle Scholar
  252. 252.
    Tian JH, Das S, Sheng ZH. Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Muncl8. J Biol Chem 2003; 278(28):26265–74.PubMedCrossRefGoogle Scholar
  253. 253.
    Cabaniols JP, Ravichandran V, Roche PA. Phosphorylation of SNAP-23 by the novel kinase SNAK regulates t-SNARE complex assembly. Mol Biol Cell 1999; 10(12):4033–41.PubMedGoogle Scholar
  254. 254.
    Hepp R, Puri N, Hohenstein AC et al. Phosphorylation of SNAP-23 regulates exocytosis from mast cells. J Biol Chem 2005; 280(8):6610–20.PubMedCrossRefGoogle Scholar
  255. 255.
    Polgar J, Lane WS, Chung SH et al. Phosphorylation of SNAP-23 in activated human platelets. J Biol Chem 2003; 278(45):44369–76.PubMedCrossRefGoogle Scholar
  256. 256.
    Matsushita K, Morrell CN, Cambien B et al. Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell 2003; 115(2):139–50.PubMedCrossRefGoogle Scholar
  257. 257.
    Beckers CJ, Balch WE. Calcium and GTP: Essential components in vesicular trafficking between the endoplasmic reticulum and Golgi apparatus. J Cell Biol 1989; 108(4):1245–56.PubMedCrossRefGoogle Scholar
  258. 258.
    Chen JL, Ahluwalia JP, Stamnes M. Selective effects of calcium chelators on anterograde and retrograde protein transport in the cell. J Biol Chem 2002; 277(38):35682–7.PubMedCrossRefGoogle Scholar
  259. 259.
    Rexach MF, Schekman RW. Distinct biochemical requirements for the budding, targeting, and fusion of ER-derived transport vesicles. J Cell Biol 1991; 114(2):219–29.PubMedCrossRefGoogle Scholar
  260. 260.
    Mills IG, Urbe S, Clague MJ. Relationships between EEA1 binding partners and their role in endosome fusion. J Cell Sci 2001; 114(Pt 10):1959–65.PubMedGoogle Scholar
  261. 261.
    Peters C, Mayer A. Ca2+/calmodulin signals the completion of docking and triggers a late step of vacuole fusion. Nature 1998; 396(6711):575–80.PubMedCrossRefGoogle Scholar
  262. 262.
    Porat A, Elazar Z. Regulation of intra-Golgi membrane transport by calcium. J Biol Chem 2000; 275(38):29233–7.PubMedCrossRefGoogle Scholar
  263. 263.
    Colombo MI, Beron W, Stahl PD. Calmodulin regulates endosome fusion. J Biol Chem 1997; 272(12):7707–12.PubMedCrossRefGoogle Scholar
  264. 264.
    Burgoyne RD, Clague MJ. Calcium and calmodulin in membrane fusion. Biochim Biophys Acta 2003; 1641(2–3):137–43.PubMedGoogle Scholar
  265. 265.
    Garner CC, Kindler S, Gundelflnger ED. Molecular determinants of presynaptic active zones. Curr Opin Neurobiol 2000; 10(3):321–7.PubMedCrossRefGoogle Scholar
  266. 266.
    Klenchin VA, Martin TF. Priming in exocytosis: Attaining fusion-competence after vesicle docking. Biochimie 2000; 82(5):399–407.PubMedCrossRefGoogle Scholar
  267. 267.
    Sabatini BL, Regehr WG. Timing of neurotransmission at fast synapses in the mammalian brain. Nature 1996; 384(6605):170–2.PubMedCrossRefGoogle Scholar
  268. 268.
    Heidelberger R, Heinemann C, Neher E et al. Calcium dependence of the rate of exocytosis in a synaptic terminal. Nature 1994; 371(6497):513–5.PubMedCrossRefGoogle Scholar
  269. 269.
    Barrett EF, Stevens CF. The kinetics of transmitter release at the frog neuromuscular junction. J Physiol 1972; 227(3):691–708.PubMedGoogle Scholar
  270. 270.
    Goda Y, Stevens CF. Two components of transmitter release at a central synapse. Proc Natl Acad Sci USA 1994; 91(26):12942–6.PubMedCrossRefGoogle Scholar
  271. 271.
    Aduri PP, Regehr WG. Delayed release of neurotransmitter from cerebellar granule cells. J Neurosci 1998; 18(20):82l4–27.Google Scholar
  272. 272.
    Hagler Jr DJ, Goda Y. Properties of synchronous and asynchronous release during pulse train depression in cultured hippocampal neurons. J Neurophysiol 2001; 85(6):2324–34.PubMedGoogle Scholar
  273. 273.
    Brose N, Petrenko AG, Sudhof TC et al. Synaptotagmin: A calcium sensor on the synaptic vesicle surface. Science 1992; 256(5059):1021–25.PubMedCrossRefGoogle Scholar
  274. 274.
    Perin MS, Fried VA, Mignery GA et al. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature 1990; 345(6272):260–3.PubMedCrossRefGoogle Scholar
  275. 275.
    Perin MS, Brose N, Jahn R et al. Domain structure of synaptotagmin (p65). J Biol Chem 1991; 266(l):623–9.PubMedGoogle Scholar
  276. 276.
    Corbalan-Garcia S, Rodriguez-Alfaro JA, Gomez-Fernandez JC. Determination of the calcium-binding membrane. Biochem J 1999; 337(Pt 3):513–21.PubMedCrossRefGoogle Scholar
  277. 277.
    Ubach J, Zhang X, Shao X et al. Ca2+ binding to synaptotagmin: How many Ca2+ ions bind to the tip of a C2-domain? EMBO J 1998; 17(l4):3921–30.PubMedCrossRefGoogle Scholar
  278. 278.
    Fernandez I, Arac D, Ubach J et al. Three-dimensional structure of the synaptotagmin 1 C2B-domain: Synaptotagmin 1 as a phospholipid binding machine. Neuron 2001; 32(6):1057–69.PubMedCrossRefGoogle Scholar
  279. 279.
    Schneggenburger R, Neher E. Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 2000; 406(6798):889–93.PubMedCrossRefGoogle Scholar
  280. 280.
    Bollmann JH, Sakmann B, Borst JG. Calcium sensitivity of glutamate release in a calyx-type terminal. Science 2000; 289(5481):953–7.PubMedCrossRefGoogle Scholar
  281. 281.
    DiAntonio A, Parfitt KD, Schwarz TL. Synaptic transmission persists in synaptotagmin mutants of Drosophila. Cell 1993; 73(7):1281–90.PubMedCrossRefGoogle Scholar
  282. 282.
    Littleton JT, Stern M, Schulze K et al. Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release. Cell 1993; 74(6):1125–34.PubMedCrossRefGoogle Scholar
  283. 283.
    Nonet ML, Grundahl K, Meyer BJ et al. Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin. Cell 1993; 73(7):1291–1305.PubMedCrossRefGoogle Scholar
  284. 284.
    Geppert M, Goda Y, Hammer RE et al. Synaptotagmin I: A major Ca2+ sensor for transmitter release at a central synapse. Cell 1994; 79(4):717–27.PubMedCrossRefGoogle Scholar
  285. 285.
    Geppert M, Goda Y, Stevens CF et al. The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature 1997; 387(6635):810–4.PubMedCrossRefGoogle Scholar
  286. 286.
    Aravamudan B, Fergestad T, Davis WS et al. Drosophila UNC-13 is essential for synaptic transmission. Nat Neurosci 1999; 2(11):965–71.PubMedCrossRefGoogle Scholar
  287. 287.
    Voets T, Moser T, Lund PE et al. Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I. Proc Nad Acad Sci USA 2001; 98(20):11680–5.CrossRefGoogle Scholar
  288. 288.
    DiAntonio A, Schwarz TL. The effect on synaptic physiology of synaptotagmin mutations in Drosophila. Neuron 1994; 12(4):909–20.PubMedCrossRefGoogle Scholar
  289. 289.
    Littleton JT, Stern M, Perin M et al. Calcium dependence of neurotransmitter release and rate of USA 1994; 91(23):10888–92.Google Scholar
  290. 290.
    Littleton JT, Serano TL, Rubin GM et al. Synaptic function modulated by changes in the ratio of synaptotagmin I and IV. Nature 1999; 400(6746):757–60.PubMedCrossRefGoogle Scholar
  291. 291.
    Morimoto T, Wang XH, Poo MM. Overexpression of synaptotagmin modulates short-term synaptic plasticity at developing neuromuscular junctions. Neuroscience 1998; 82(4):969–78.PubMedCrossRefGoogle Scholar
  292. 292.
    Yoshihara M, Litdeton JT. Synaptotagmin I functions as a calcium sensor to synchronize neurotransmitter release. Neuron 2002; 36(5):897–908.PubMedCrossRefGoogle Scholar
  293. 293.
    Tucker WC, Chapman ER. Role of synaptotagmin in Ca2+-triggered exocytosis. Biochem J 2002; 366(Pt 1):1–13.PubMedGoogle Scholar
  294. 294.
    von Poser C, Ichtchenko K, Shao X et al. The evolutionary pressure to inactivate. A subclass of synaptotagmins with an amino acid substitution that abolishes Ca2+ binding. J Biol Chem 1997; 272(22):14314–9.CrossRefGoogle Scholar
  295. 295.
    Bai J, Wang P, Chapman ER. C2A activates a cryptic Ca(2+)-triggered membrane penetration activity within the C2B domain of synaptotagmin I. Proc Nad Acad Sci USA 2002; 99(3):1665–70.CrossRefGoogle Scholar
  296. 296.
    Desai RC, Vyas B, Earles CA et al. The C2B domain of synaptotagmin is a Ca(2+)-sensing module essential for exocytosis. J Cell Biol 2000; 150(5):1125–36.PubMedCrossRefGoogle Scholar
  297. 297.
    Darner CK, Creutz CE. Calcium-dependent self-association of synaptotagmin I. J Neurochem 1996; 67(4):1661–8.Google Scholar
  298. 298.
    Schoch S, Castillo PE, Jo T et al. RIM1alpha forms a protein scaffold for regulating neurotransmitter release at the active zone. Nature 2002; 4l5(6869):321–6.CrossRefGoogle Scholar
  299. 299.
    Fukuda M, Mikoshiba K. Distinct self-oligomerization activities of synaptotagmin family. Unique calcium-dependent oligomerization properties of synaptotagmin VII. J Biol Chem 2000; 275(36):28180–5.PubMedGoogle Scholar
  300. 300.
    Osborne SL, Herreros J, Bastiaens PI et al. Calcium-dependent oligomerization of synaptotagmins I and II. Synaptotagmins I and II are localized on the same synaptic vesicle and heterodimerize in the presence of calcium. J Biol Chem 1999; 274(l):59–66.PubMedCrossRefGoogle Scholar
  301. 301.
    Mahal LK, Sequeira SM, Gureasko JM et al. Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I. J Cell Biol 2002; 158(2):273–82.PubMedCrossRefGoogle Scholar
  302. 302.
    Chapman ER, Davis AF. Direct interaction of a Ca2+-binding loop of synaptotagmin with lipid bilayers. J Biol Chem 1998; 273(22):13995–14001.PubMedCrossRefGoogle Scholar
  303. 303.
    Davis AF, Bai J, Fasshauer D et al. Kinetics of synaptotagmin responses to Ca2+ and assembly with the core SNARE complex onto membranes. Neuron 1999; 24(2):363–76.PubMedCrossRefGoogle Scholar
  304. 304.
    Bai J, Earles CA, Lewis JL et al. Membrane-embedded synaptotagmin penetrates cis or trans target membranes and clusters via a novel mechanism. J Biol Chem 2000; 275(33):25427–35.PubMedCrossRefGoogle Scholar
  305. 305.
    Fernandez-Chacon R, Konigstorfer A, Gerber SH et al. Synaptotagmin I functions as a calcium regulator of release probability. Nature 2001; 4l0(6824):4l–9.Google Scholar
  306. 306.
    Robinson IM, Ranjan R, Schwarz TL. Synaptotagmins I and IV promote transmitter release independendy of Ca(2+) binding in the C(2)A domain. Nature 2002; 4l8(6895):336–40.CrossRefGoogle Scholar
  307. 307.
    Shin OH, Rhee JS, Tang J et al. Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. Neuron 2003; 37(1):99–108.PubMedCrossRefGoogle Scholar
  308. 308.
    Madder JM, Drummond JA, Loewen CA et al. The C(2)B Ca(2+)-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature 2002; 4l8(6895):340–4.Google Scholar
  309. 309.
    Wang CT, Lu JC, Bai J et al. Different domains of synaptotagmin control the choice between kiss-and-run and full fusion. Nature 2003; 424(6951):943–7.PubMedCrossRefGoogle Scholar
  310. 310.
    Bennett MK, Calakos N, Scheller RH. Syntaxin: A synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 1992; 257(5067):255–9.PubMedCrossRefGoogle Scholar
  311. 311.
    Sollner T, Bennett MK, Whiteheart SW et al. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 1993; 75(3):409–18.PubMedCrossRefGoogle Scholar
  312. 312.
    Chapman ER, Hanson PI, An S et al. Ca2+ regulates the interaction between synaptotagmin and syntaxin 1. J Biol Chem 1995; 270(40):23667–71.PubMedCrossRefGoogle Scholar
  313. 313.
    Li C, Ullrich B, Zhang JZ et al. Ca(2+)-dependent and-independent activities of neural and nonneural synaptotagmins. Nature 1995; 375(6532):594–9.CrossRefGoogle Scholar
  314. 314.
    Schiavo G, Stenbeck G, Rothman JE et al. Binding of the synaptic vesicle v-SNARE, synaptotagmin, to the plasma membrane t-SNARE, SNAP-25, can explain docked vesicles at neurotoxin-treated synapses. Proc Natl Acad Sci USA 1997; 94(3):997–1001.PubMedCrossRefGoogle Scholar
  315. 315.
    Earles CA, Bai J, Wang P et al. The tandem C2 domains of synaptotagmin contain redundant Ca2+ binding sites that cooperate to engage t-SNAREs and trigger exocytosis. J Cell Biol 2001; 154(6):1117–23.PubMedCrossRefGoogle Scholar
  316. 316.
    Gerona RR, Larsen EC, Kowalchyk JA et al. The C terminus of SNAP25 is essential for Ca(2+)-dependent binding of synaptotagmin to SNARE complexes. J Biol Chem 2000; 275(9):6328–36.PubMedCrossRefGoogle Scholar
  317. 317.
    Zhang X, Kim-Miller MJ, Fukuda M et al. Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis. Neuron 2002; 34(4):599–611.PubMedCrossRefGoogle Scholar
  318. 318.
    Sutton RB, Ernst JA, Brunger AT. Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca(+2)-independent snare complex interaction. J Cell Biol 1999; l47(3):589–98.CrossRefGoogle Scholar
  319. 319.
    Littleton JT, Bai J, Vyas B et al. Synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+-triggered fusion and recycling of synaptic vesicles in vivo. J Neurosci 2001; 21(5):l421–33.Google Scholar
  320. 320.
    Chapman ER, An S, Edwardson JM et al. A novel function for the second C2 domain of synaptotagmin. Ca2+-triggered dimerization. J Biol Chem 1996; 271(10):5844–9.PubMedCrossRefGoogle Scholar
  321. 321.
    Ann K, Kowalchyk JA, Loyet KM et al. Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-activated exocytosis. J Biol Chem 1997; 272(32):19637–40.PubMedCrossRefGoogle Scholar
  322. 322.
    Loyet KM, Kowalchyk JA, Chaudhary A et al. Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phosphoinositide effector protein for regulated exocytosis. J Biol Chem 1998; 273(l4):8337–43.PubMedCrossRefGoogle Scholar
  323. 323.
    Berwin B, Floor E, Martin TF. CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-core vesicle exocytosis. Neuron 1998; 21(l):137–45.PubMedCrossRefGoogle Scholar
  324. 324.
    Tandon A, Bannykh S, Kowalchyk JA et al. Differential regulation of exocytosis by calcium and CAPS in semi-intact synaptosomes. Neuron 1998; 21(1):147–54.PubMedCrossRefGoogle Scholar
  325. 325.
    Renden R, Berwin B, Davis W et al. Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion. Neuron 2001; 31(3):421–37.PubMedCrossRefGoogle Scholar
  326. 326.
    Grishanin RN, Klenchin VA, Loyet KM et al. Membrane association domains in Ca2+-dependent activator protein for secretion mediate plasma membrane and dense-core vesicle binding required for Ca2+-dependent exocytosis. J Biol Chem 2002; 277(24):22025–34.PubMedCrossRefGoogle Scholar
  327. 327.
    Grishanin RN, Kowalchyk JA, Klenchin VA et al. CAPS acts at a prefusion step in dense-core vesicle exocytosis as a PIP2 binding protein. Neuron 2004; 43(4):551–62.PubMedCrossRefGoogle Scholar
  328. 328.
    Bhattacharya S, Stewart BA, Niemeyer BA et al. Members of the synaptobrevin/vesicle-associated membrane protein (VAMP) family in Drosophila are functionally interchangeable in vivo for neurotransmitter release and cell viability. Proc Natl Acad Sci USA 2002; 99(21):13867–72.PubMedCrossRefGoogle Scholar
  329. 329.
    Sorensen JB, Nagy G, Varoqueaux F et al. Differential control of the releasable vesicle pools by SNAP-25 splice variants and SNAP-23. Cell 2003; ll4(l):75–86.CrossRefGoogle Scholar
  330. 330.
    Chieregatti E, Chicka MC, Chapman ER et al. SNAP-23 functions in docking/fusion of granules at low Ca2+. Mol Biol Cell 2004; 15(4):1918–30.PubMedCrossRefGoogle Scholar
  331. 331.
    Rossi V, Picco R, Vacca M et al. VAMP subfamilies identified by specific R-SNARE motifs. Biol Cell 2004; 96(4):251–6.PubMedCrossRefGoogle Scholar
  332. 332.
    Chen Y, Xu Y, Zhang F et al. Constitutive versus regulated SNARE assembly: A structural basis. EMBO J 2004; 23(4):681–9.PubMedCrossRefGoogle Scholar
  333. 333.
    Hay JC, Scheller RH. SNAREs and NSF in targeted membrane fusion. Curr Opin Cell Biol 1997; 9(4):505–12.PubMedCrossRefGoogle Scholar
  334. 334.
    Chen D, Bernstein AM, Lemons PP et al. Molecular mechanisms of platelet exocytosis: Role of SNAP-23 and syntaxin 2 in dense core granule release. Blood 2000; 95(3):921–9.PubMedGoogle Scholar
  335. 335.
    Quinones B, Riento K, Olkkonen VM et al. Syntaxin 2 splice variants exhibit differential expression patterns, biochemical properties and subcellular localizations. J Cell Sci 1999; 112(Pt 23):4291–304.PubMedGoogle Scholar
  336. 336.
    Katafuchi K, Mori T, Toshimori K et al. Localization of a syntaxin isoform, syntaxin 2, to the acrosomal region of rodent spermatozoa. Mol Reprod Dev 2000; 57(4):375–83.PubMedCrossRefGoogle Scholar
  337. 337.
    Low SH, Li X, Miura M et al. Syntaxin 2 and endobrevin are required for the terminal step of cytokinesis in mammalian cells. Dev Cell 2003; 4(5):753–9.PubMedCrossRefGoogle Scholar
  338. 338.
    Abonyo BO, Gou D, Wang P et al. Syntaxin 2 and SNAP-23 are required for regulated surfactant secretion. Biochemistry 2004; 43(12):3499–506.PubMedCrossRefGoogle Scholar
  339. 339.
    Morgans CW, Brandstatter JH, Kellerman J et al. A SNARE complex containing syntaxin 3 is present in ribbon synapses of the retina. J Neurosci 1996; 16(21):6713–21.PubMedGoogle Scholar
  340. 340.
    Breuza L, Fransen J, Le Bivic A. Transport and function of syntaxin 3 in human epithelial intestinal cells. Am J Physiol Cell Physiol 2000; 279(4):C1239–48.PubMedGoogle Scholar
  341. 341.
    Paumet F, Le Mao J, Martin S et al. Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: Functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment. J Immunol 2000; 164(11):5850–7.PubMedGoogle Scholar
  342. 342.
    Min J, Okada S, Kanzaki M et al. Synip: A novel insulin-regulated syntaxin 4-binding protein mediating GLUT4 translocation in adipocytes. Mol Cell 1999; 3(6):751–60.PubMedCrossRefGoogle Scholar
  343. 343.
    Flaumenhaft R, Croce K, Chen E et al. Proteins of the exocytotic core complex mediate platelet alpha-granule secretion. Roles of vesicle-associated membrane protein, SNAP-23, and syntaxin 4. J Biol Chem 1999; 274(4):2492–501.PubMedCrossRefGoogle Scholar
  344. 344.
    Fu J, Naren AP, Gao X et al. Protease-activated receptor-1 activation of endothelial cells induces protein kinase Calpha-dependent phosphorylation of syntaxin 4 and Muncl8c: Role in signaling p-selectin expression. J Biol Chem 2005; 280(5):3178–84.PubMedCrossRefGoogle Scholar
  345. 345.
    Hay JC, Klumperman J, Oorschot V et al. Localization, dynamics, and protein interactions reveal distinct roles for ER and Golgi SNAREs. J Cell Biol 1998; 141(7):1489–502.PubMedCrossRefGoogle Scholar
  346. 346.
    Rowe T, Dascher C, Bannykh S et al. Role of vesicle-associated syntaxin 5 in the assembly of preGolgi intermediates. Science 1998; 279(5351):696–700.PubMedCrossRefGoogle Scholar
  347. 347.
    Wong SH, Xu Y, Zhang T et al. Syntaxin 7, a novel syntaxin member associated with the early endosomal compartment. J Biol Chem 1998; 273(1):375–80.PubMedCrossRefGoogle Scholar
  348. 348.
    Prekeris R, Yang B, Oorschot V et al. Differential roles of syntaxin 7 and syntaxin 8 in endosomal trafficking. Mol Biol Cell 1999; 10(11):3891–908.PubMedGoogle Scholar
  349. 349.
    Ward DM, Pevsner J, Scullion MA et al. Syntaxin 7 and VAMP-7 are soluble N-ethylmaleimide-sensitive factor attachment protein receptors required for late endosome-lysosome and homotypic lysosome fusion in alveolar macrophages. Mol Biol Cell 2000; 11(7):2327–33.PubMedGoogle Scholar
  350. 350.
    Mullock BM, Smith CW, Ihrke G et al. Syntaxin 7 is localized to late endosome compartments, associates with Vamp 8, and Is required for late endosome-lysosome fusion. Mol Biol Cell 2000; 11(9):3137–53.PubMedGoogle Scholar
  351. 351.
    Valdez AC, Cabaniols JP, Brown MJ et al. Syntaxin 11 is associated with SNAP-23 on late endosomes and the trans-Golgi network. J Cell Sci 1999; 112(Pt 6):845–54.PubMedGoogle Scholar
  352. 352.
    Prekeris R, Klumperman J, Scheller RH. Syntaxin 11 is an atypical SNARE abundant in the immune system. Eur J Cell Biol 2000; 79(11):771–80.PubMedCrossRefGoogle Scholar
  353. 353.
    Hirling H, Steiner P, Chaperon C et al. Syntaxin 13 is a developmentally regulated SNARE involved in neurite outgrowth and endosomal trafficking. Eur J Neurosci 2000; 12(6): 1913–23.PubMedCrossRefGoogle Scholar
  354. 354.
    Huang L, Kuo YM, Gitschier J. The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency. Nat Genet 1999; 23(3):329–32.PubMedCrossRefGoogle Scholar
  355. 355.
    Prekeris R, Klumperman J, Chen YA et al. Syntaxin 13 mediates cycling of plasma membrane proteins via tubulovesicular recycling endosomes. J Cell Biol 1998; 143(4):957–71.PubMedCrossRefGoogle Scholar
  356. 356.
    Tang BL, Low DY, Lee SS et al. Molecular cloning and localization of human syntaxin 16, a member of the syntaxin family of SNARE proteins. Biochem Biophys Res Commun 1998; 242(3):673–9.PubMedCrossRefGoogle Scholar
  357. 357.
    Simonsen A, Bremnes B, Ronning E et al. Syntaxin-16, a putative Golgi t-SNARE. Eur J Cell Biol 1998; 75(3):223–31.PubMedGoogle Scholar
  358. 358.
    Mallard F, Tang BL, Galli T et al. Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. J Cell Biol 2002; 156(4):653–64.PubMedCrossRefGoogle Scholar
  359. 359.
    Xu H, Boulianne GL, Trimble WS. Drosophila syntaxin 16 is a Q-SNARE implicated in Golgi dynamics. J Cell Sci 2002; 115(Pt 23):4447–55.PubMedCrossRefGoogle Scholar
  360. 360.
    Steegmaier M, Oorschot V, Klumperman J et al. Syntaxin 17 is abundant in steroidogenic cells and implicated in smooth endoplasmic reticulum membrane dynamics. Mol Biol Cell 2000; 11(8):2719–31.PubMedGoogle Scholar
  361. 361.
    Hatsuzawa K, Hirose H, Tani K et al. Syntaxin 18, a SNAP receptor that functions in the endoplasmic reticulum, intermediate compartment, and cis-Golgi vesicle trafficking. J Biol Chem 2000; 275(18):13713–20.PubMedCrossRefGoogle Scholar
  362. 362.
    Xu Y, Wong SH, Tang BL et al. A 29-kilodalton Golgi soluble N-ethylmaleimide-sensitive factor attachment protein receptor (Vtil-rp2) implicated in protein trafficking in the secretory pathway. J Biol Chem 1998; 273(34):21783–9.PubMedCrossRefGoogle Scholar
  363. 363.
    Antonin W, Riedel D, von Mollard GF. The SNARE Vtila-beta is localized to small synaptic vesicles and participates in a novel SNARE complex. J Neurosci 2000; 20(15):5724–32.PubMedGoogle Scholar
  364. 364.
    Kreykenbohm V, Wenzel D, Antonin W et al. The SNAREs vtila and vtilb have distinct localization and SNARE complex partners. Eur J Cell Biol 2002; 81(5):273–80.PubMedCrossRefGoogle Scholar
  365. 365.
    Chidambaram S, Mullers N, Wiederhold K et al. Specific interaction between SNAREs and epsin N-terminal homology (ENTH) domains of epsin-related proteins in trans-Golgi network to endosome transport. J Biol Chem 2004; 279(6):4l75–9.Google Scholar
  366. 366.
    Burri L, Lithgow T. A complete set of SNAREs in yeast. Traffic 2004; 5(l):45–52.PubMedCrossRefGoogle Scholar
  367. 367.
    Nakajima K, Hirose H, Taniguchi M et al. Involvement of BNIP1 in apoptosis and endoplasmic reticulum membrane fusion. EMBO J 2004; 23(16):32l6–26.CrossRefGoogle Scholar
  368. 368.
    Charest A, Lane K, McMahon K et al. Association of a novel PDZ domain-containing peripheral Golgi protein with the Q-SNARE protein syntaxin 6. J Biol Chem 2001; 276:29456–5.PubMedCrossRefGoogle Scholar
  369. 369.
    Martin-Martin B, Nabokina SM, Blasi J et al. Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis. Blood 2000; 96(7):2574–83.PubMedGoogle Scholar
  370. 370.
    Simonsen A, Gaullier JM, D’Arrigo A et al. The Rab5 effector EEA1 interacts direcdy with syntaxin-6. J Biol Chem 1999; 274(41):28857–60.PubMedCrossRefGoogle Scholar
  371. 371.
    Wendler F, Page L, Urbe S et al. Homotypic fusion of immature secretory granules during maturation requires syntaxin 6. Mol Biol Cell 2001; 12(6):1699–709.PubMedGoogle Scholar
  372. 372.
    Kuliawat R, Kalinina E, Bock J et al. Syntaxin-6 SNARE involvement in secretory and endocytic pathways of cultured pancreatic beta-cells. Mol Biol Cell 2004; 15(4):1690–701.PubMedCrossRefGoogle Scholar
  373. 373.
    Murray RZ, Wylie FG, Khromykh T et al. Syntaxin 6 and Vtilb form a novel SNARE complex, which is up-regulated in activated macrophages to facilitate exocytosis of tumor necrosis Factor-alpha. J Biol Chem 2005; 280(11):10478–83.PubMedCrossRefGoogle Scholar
  374. 374.
    Subramaniam VN, Loh E, Horstmann H et al. Preferential association of syntaxin 8 with the early endosome. J Cell Sci 2000; 113(Pt 6):997–1008.PubMedGoogle Scholar
  375. 375.
    Tang BL, Low DY, Tan AE et al. Syntaxin 10: A member of the syntaxin family localized to the trans-Golgi network. Biochem Biophys Res Commun 1998; 242(2):345–50.PubMedCrossRefGoogle Scholar
  376. 376.
    Zhang T, Wong SH, Tang BL et al. The mammalian protein (rbetl) homologous to yeast Betlp is primarily associated with the preGolgi intermediate compartment and is involved in vesicular transport from the endoplasmic reticulum to the Golgi apparatus. J Cell Biol 1997; 139(5): 1157–68.PubMedCrossRefGoogle Scholar
  377. 377.
    Xu Y, Wong SH, Zhang T et al. GS15, a 15-kilodalton Golgi soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) homologous to rbetl. J Biol Chem 1997; 272(32):20162–6.PubMedCrossRefGoogle Scholar
  378. 378.
    Xu Y, Martin S, James DE et al. GS15 forms a SNARE complex with syntaxin 5, GS28, and Ykt6 and is implicated in traffic in the early cisternae of the Golgi apparatus. Mol Biol Cell 2002; 13(10):3493–507.PubMedCrossRefGoogle Scholar
  379. 379.
    Chen D, Bernstein AM, Lemons PP et al. Molecular mechanisms of platelet exocytosis: Role of SNAP-23 and syntaxin 2 in dense core granule release. Blood 2000; 95(3):921–9.PubMedGoogle Scholar
  380. 380.
    Gaisano HY, Sheu L, Wong PP et al. SNAP-23 is located in the basolateral plasma membrane of rat pancreatic acinar cells. FEBS Lett 1997; 4l4(2):298–302.CrossRefGoogle Scholar
  381. 381.
    Leung SM, Chen D, DasGupta BR et al. SNAP-23 requirement for transferrin recycling in Streptolysin-O-permeabilized Madin-Darby canine kidney cells. J Biol Chem 1998; 273(28):17732–41.PubMedCrossRefGoogle Scholar
  382. 382.
    Guo Z, Turner C, Casde D. Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells. Cell 1998; 94(4):537–48.PubMedCrossRefGoogle Scholar
  383. 383.
    Steegmaier M, Yang B, Yoo JS et al. Three novel proteins of the syntaxin/SNAP-25 family. J Biol Chem 1998; 273(51):34l71–9.CrossRefGoogle Scholar
  384. 384.
    Wong SH, Xu Y, Zhang T et al. GS32, a novel Golgi SNARE of 32 kDa, interacts preferentially with syntaxin 6. Mol Biol Cell 1999; 10(1):119–34.PubMedGoogle Scholar
  385. 385.
    Hohenstein AC, Roche PA. SNAP-29 is a promiscuous syntaxin-binding SNARE. Biochem Biophys Res Commun 2001; 285(2):167–71.PubMedCrossRefGoogle Scholar
  386. 386.
    Su Q, Mochida S, Tian JH et al. SNAP-29: A general SNARE protein that inhibits SNARE disassembly and is implicated in synaptic transmission. Proc Natl Acad Sci USA 2001; 98(24):14038–43.PubMedCrossRefGoogle Scholar
  387. 387.
    Steegmaier M, Klumperman J, Foletti DL et al. Vesicle-associated membrane protein 4 is implicated in trans-Golgi network vesicle trafficking. Mol Biol Cell 1999; 10(6):1957–72.PubMedGoogle Scholar
  388. 388.
    Peden AA, Park GY, Scheller RH. The Di-leucine motif of vesicle-associated membrane protein 4 is required for its localization and AP-1 binding. J Biol Chem 2001; 276(52):49183–7.PubMedCrossRefGoogle Scholar
  389. 389.
    Zeng Q, Subramaniam VN, Wong SH et al. A novel synaptobrevin/VAMP homologous protein (VAMP5) is increased during in vitro myogenesis and present in the plasma membrane. Mol Biol Cell 1998; 9(9):2423–37.PubMedGoogle Scholar
  390. 390.
    Advani RJ, Yang B, Prekeris R et al. VAMP-7 mediates vesicular transport from endosomes to lysosomes. J Cell Biol 1999; 146(4):765–76.PubMedCrossRefGoogle Scholar
  391. 391.
    Lafont F, Verkade P, Galli T et al. Raft association of SNAP receptors acting in apical trafficking in Madin-Darby canine kidney cells. Proc Natl Acad Sci USA 1999; 96(7):3734–8.PubMedCrossRefGoogle Scholar
  392. 392.
    Nagamatsu S, Nakamichi Y, Watanabe T et al. Localization of cellubrevin-related peptide, endobrevin, in the early endosome in pancreatic beta cells and its physiological function in exo-Endocytosis of secretory granules. J Cell Sci 2001; 114(Pt l):219–27.PubMedGoogle Scholar
  393. 393.
    Steegmaier M, Lee KC, Prekeris R et al. SNARE protein trafficking in polarized MDCK cells. Traffic 2000; l(7):553–60.CrossRefGoogle Scholar
  394. 394.
    Polgar J, Chung SH, Reed GL. Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion. Blood 2002; 100(3):1081–3.PubMedCrossRefGoogle Scholar
  395. 395.
    Wang CC, Ng CP, Lu L et al. A role of VAMP8/endobrevin in regulated exocytosis of pancreatic acinar cells. Dev Cell 2004; 7(3):359–71.PubMedCrossRefGoogle Scholar
  396. 396.
    Zhang T, Hong W. Ykt6 forms a SNARE complex with syntaxin 5, GS28 and Betl and participates in a late stage in ER-Golgi transport. J Biol Chem 2001; 276:27480–7.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Division of Biological Sciences and Center for Structural and Functional NeuroscienceThe University of MontanaMissoulaUSA
  2. 2.Institute of Biochemistry II Frankfurt Medical SchoolUniversity HospitalFrankfurtGermany

Personalised recommendations