PtdIns(4)P Signalling and Recognition Systems

  • Marc Lenoir
  • Michael OverduinEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 991)


The Golgi apparatus is a sorting platform that exchanges extensively with the endoplasmic reticulum (ER), endosomes (Es) and plasma membrane (PM) compartments. The last compartment of the Golgi, the trans-Golgi Network (TGN) is a large complex of highly deformed membranes from which vesicles depart to their targeted organelles but also are harbored from retrograde pathways. The phosphoinositide (PI) composition of the TGN is marked by an important contingent of phosphatidylinositol-4-phosphate (PtdIns(4)P). Although this PI is present throughout the Golgi, its proportion grows along the successive cisternae and peaks at the TGN. The levels of this phospholipid are controlled by a set of kinases and phosphatases that regulate its concentrations in the Golgi and maintain a dynamic gradient that determines the cellular localization of several interacting proteins. Though not exclusive to the Golgi, the synthesis of PtdIns(4)P in other membranes is relatively marginal and has unclear consequences. The significance of PtdIns(4)P within the TGN has been demonstrated for numerous cellular events such as vesicle formation, lipid metabolism, and membrane trafficking.


PtdIns(4)P Golgi Phosphoinositide PH domain Cellular trafficking Membrane 


  1. 1.
    Barylko B, Gerber SH, Binns DD et al (2001) A novel family of phosphatidylinositol 4-kinases conserved from yeast to humans. J Biol Chem 276:7705–7708PubMedGoogle Scholar
  2. 2.
    Minogue S, Anderson JS, Waugh MG et al (2001) Cloning of a human type II phosphatidylinositol 4-kinase reveals a novel lipid kinase family. J Biol Chem 276:16635–16640PubMedGoogle Scholar
  3. 3.
    Wang YJ, Wang J, Sun HQ et al (2003) Phosphatidylinositol 4 phosphate regulates targeting of clathrin adaptor AP-1 complexes to the Golgi. Cell 114:299–310PubMedGoogle Scholar
  4. 4.
    Wei YJ, Sun HQ, Yamamoto M et al (2002) Type II phosphatidylinositol 4-kinase beta is a cytosolic and peripheral membrane protein that is recruited to the plasma membrane and activated by Rac-GTP. J Biol Chem 277:46586–46593PubMedGoogle Scholar
  5. 5.
    Wong K, Meyers d R, Cantley LC (1997) Subcellular locations of phosphatidylinositol 4-kinase isoforms. J Biol Chem 272:13236–13241PubMedGoogle Scholar
  6. 6.
    Godi A, Pertile P, Meyers R et al (1999) ARF mediates recruitment of PtdIns-4-OH kinase-beta and stimulates synthesis of PtdIns(4,5)P2 on the Golgi complex. Nat Cell Biol 1:280–287PubMedGoogle Scholar
  7. 7.
    Balla T, Downing GJ, Jaffe H et al (1997) Isolation and molecular cloning of wortmannin-sensitive bovine type III phosphatidylinositol 4-kinases. J Biol Chem 272:18358–18366PubMedGoogle Scholar
  8. 8.
    Meyers R, Cantley LC (1997) Cloning and characterization of a Wortmannin-sensitive human phosphatidylinositol 4-kinase. J Biol Chem 272:4384–4390PubMedGoogle Scholar
  9. 9.
    Rohde HM, Cheong FY, Konrad G et al (2003) The human phosphatidylinositol phosphatase SAC1 interacts with the coatomer I complex. J Biol Chem 278:52689–52699PubMedGoogle Scholar
  10. 10.
    Domin J, Gaidarov I, Smith ME et al (2000) The class II phosphoinositide 3-kinase PI3K–alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles. J Biol Chem 275:11943–11950PubMedGoogle Scholar
  11. 11.
    Domin J, Pages F, Volinia S et al (1997) Cloning of a human phosphoinositide 3-kinase with a C2 domain that displays reduced sensitivity to the inhibitor wortmannin. Biochem J 326:139–147PubMedGoogle Scholar
  12. 12.
    Yoshioka K, Yoshida K, Cui H et al (2012) Endothelial PI3K-C2[alpha], a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nat Med 18(10):1560–1569PubMedGoogle Scholar
  13. 13.
    Arcaro A, Volinia S, Zvelebil MJ et al (1998) Human phosphoinositide 3-kinase C2β, the role of calcium and the C2 domain in enzyme activity. J Biol Chem 273:33082–33090PubMedGoogle Scholar
  14. 14.
    Ono F, Nakagawa T, Saito S et al (1998) A novel class II phosphoinositide 3-kinase predominantly expressed in the liver and its enhanced expression during liver regeneration. J Biol Chem 273:7731–7736PubMedGoogle Scholar
  15. 15.
    Wu Y, Dowbenko D, Pisabarro MT et al (2001) PTEN 2, a golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase. J Biol Chem 276:21745–21753PubMedGoogle Scholar
  16. 16.
    Wu Y, Dowbenko D, Spencer S et al (2000) Interaction of the tumor suppressor PTEN/MMAC with a PDZ domain of MAGI3, a novel membrane-associated guanylate kinase. J Biol Chem 275:21477–21485PubMedGoogle Scholar
  17. 17.
    Perren A, Komminoth P, Saremaslani P et al (2000) Mutation and expression analyses reveal differential subcellular compartmentalization of PTEN in endocrine pancreatic tumors compared to normal islet cells. Am J Pathol 157:1097–1103PubMedGoogle Scholar
  18. 18.
    Ishihara H, Shibasaki Y, Kizuki N et al (1998) Type I phosphatidylinositol-4-phosphate 5-kinases. Cloning of the third isoform and deletion/substitution analysis of members of this novel lipid kinase family. J Biol Chem 273:8741–8748PubMedGoogle Scholar
  19. 19.
    Ishihara H, Shibasaki Y, Kizuki N et al (1996) Cloning of cDNAs encoding two isoforms of 68-kDa type I phosphatidylinositol4-phosphate 5-kinase. J Biol Chem 271:23611–23614PubMedGoogle Scholar
  20. 20.
    Loijens JC, Anderson RA (1996) Type I phosphatidylinositol-4-phosphate 5-kinases are distinct members of this novel lipid kinase family. J Biol Chem 271:32937–32943PubMedGoogle Scholar
  21. 21.
    Ooms LM, Horan KA, Rahman P et al (2009) The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease. Biochem J 419:29–49PubMedGoogle Scholar
  22. 22.
    Ungewickell A, Ward ME, Ungewickell E et al (2004) The inositol polyphosphate 5-phosphatase Ocrl associates with endosomes that are partially coated with clathrin. Proc Natl Acad Sci U S A 101:13501–13506PubMedGoogle Scholar
  23. 23.
    Suchy SF, Olivos-Glander IM, Nussbaum RL (1995) Lowe Syndrome, a deficiency of a phosphatidyl-inositol 4,5-bisphosphate 5-phosphatase in the Golgi apparatus. Hum Mol Genet 4:2245–2250PubMedGoogle Scholar
  24. 24.
    Mochizuki Y, Takenawa T (1999) Novel inositol polyphosphate 5-phosphatase localizes at membrane ruffles. J Biol Chem 274:36790–36795PubMedGoogle Scholar
  25. 25.
    Nemoto Y, Wenk MR, Watanabe M et al (2001) Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals. J Biol Chem 276:41133–41142PubMedGoogle Scholar
  26. 26.
    Haffner C, Takei K, Chen H et al (1997) Synaptojanin 1: localization on coated endocytic intermediates in nerve terminals and interaction of its 170 kDa isoform with Eps15. FEBS Lett 419:175–180PubMedGoogle Scholar
  27. 27.
    Gurung R, Tan A, Ooms LM et al (2003) Identification of a novel domain in two mammalian inositol-polyphosphate 5-phosphatases that mediates membrane ruffle localization. J Biol Chem 278:11376–11385PubMedGoogle Scholar
  28. 28.
    Wetzker R, Klinger R, Hsuan J et al (1991) Purification and characterization of phosphatidylinositol 4-kinase from human erythrocyte membranes. Eur J Biochem 200:179–185PubMedGoogle Scholar
  29. 29.
    Nakanishi S, Catt KJ, Balla T (1995) A wortmannin-sensitive phosphatidylinositol 4-kinase that regulates hormone-sensitive pools of inositolphospholipids. Proc Natl Acad Sci U S A 92:5317–5321PubMedGoogle Scholar
  30. 30.
    Jergil B, Sundler R (1983) Phosphorylation of phosphatidylinositol in rat liver Golgi. J Biol Chem 258:7968–7973PubMedGoogle Scholar
  31. 31.
    Balla A, Tuymetova G, Barshishat M et al (2002) Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments. J Biol Chem 277:20041–20050PubMedGoogle Scholar
  32. 32.
    Minogue S, Waugh MG, De Matteis MA et al (2006) Phosphatidylinositol 4-kinase is required for endosomal trafficking and degradation of the EGF receptor. J Cell Sci 119:571–581PubMedGoogle Scholar
  33. 33.
    Lu D, Sun HQ, Wang H et al (2012) Phosphatidylinositol 4-kinase IIalpha is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner. J Biol Chem 287:21856–21865PubMedGoogle Scholar
  34. 34.
    Nishikawa K, Toker A, Wong K et al (1998) Association of protein kinase Cmu with type II phosphatidylinositol 4-kinase and type I phosphatidylinositol-4-phosphate 5-kinase. J Biol Chem 273:23126–23133PubMedGoogle Scholar
  35. 35.
    Porter FD, Li YS, Deuel TF (1988) Purification and characterization of a phosphatidylinositol 4-kinase from bovine uteri. J Biol Chem 263:8989–8995PubMedGoogle Scholar
  36. 36.
    Minogue S, Chu KM, Westover EJ et al (2010) Relationship between phosphatidylinositol 4-phosphate synthesis, membrane organization, and lateral diffusion of PI4KIIalpha at the trans-Golgi network. J Lipid Res 51:2314–2324PubMedGoogle Scholar
  37. 37.
    Banerji S, Ngo M, Lane CF et al (2010) Oxysterol binding protein-dependent activation of sphingomyelin synthesis in the Golgi apparatus requires phosphatidylinositol 4-kinase IIalpha. Mol Biol Cell 21:4141–4150PubMedGoogle Scholar
  38. 38.
    Balla A, Tuymetova G, Tsiomenko A et al (2005) A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1. Mol Biol Cell 16:1282–1295PubMedGoogle Scholar
  39. 39.
    Audhya A, Foti M, Emr SD (2000) Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Mol Biol Cell 11:2673–2689PubMedGoogle Scholar
  40. 40.
    Haynes LP, Thomas GM, Burgoyne RD (2005) Interaction of neuronal calcium sensor-1 and ADP-ribosylation factor 1 allows bidirectional control of phosphatidylinositol 4-kinase beta and trans-Golgi network-plasma membrane traffic. J Biol Chem 280:6047–6054PubMedGoogle Scholar
  41. 41.
    Hausser A, Storz P, Martens S et al (2005) Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the Golgi complex. Nat Cell Biol 7:880–886PubMedGoogle Scholar
  42. 42.
    Hausser A, Link G, Hoene M et al (2006) Phospho-specific binding of 14-3-3 proteins to phosphatidylinositol 4-kinase III β protects from dephosphorylation and stabilizes lipid kinase activity. J Cell Sci 119:3613–3621PubMedGoogle Scholar
  43. 43.
    de Graaf P, Zwart WT, van Dijken RA et al (2004) Phosphatidylinositol 4-kinasebeta is critical for functional association of rab11 with the Golgi complex. Mol Biol Cell 15:2038–2047PubMedGoogle Scholar
  44. 44.
    Whitters EA, Cleves AE, McGee TP et al (1993) SAC1p is an integral membrane protein that influences the cellular requirement for phospholipid transfer protein function and inositol in yeast. J Cell Biol 122:79–94PubMedGoogle Scholar
  45. 45.
    Blagoveshchenskaya A, Cheong FY, Rohde HM et al (2008) Integration of Golgi trafficking and growth factor signaling by the lipid phosphatase SAC1. J Cell Biol 180:803–812PubMedGoogle Scholar
  46. 46.
    Cheong FY, Sharma V, Blagoveshchenskaya A et al (2010) Spatial regulation of Golgi phosphatidylinositol-4-phosphate is required for enzyme localization and glycosylation fidelity. Traffic 11:1180–1190PubMedGoogle Scholar
  47. 47.
    Manford A, Xia T, Saxena AK et al (2010) Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function. EMBO J 29:1489–1498PubMedGoogle Scholar
  48. 48.
    Liu Y, Boukhelifa M, Tribble E et al (2008) The Sac1 phosphoinositide phosphatase regulates Golgi membrane morphology and mitotic spindle organization in mammals. Mol Biol Cell 19:3080–3096PubMedGoogle Scholar
  49. 49.
    Guo S, Stolz LE, Lemrow SM et al (1999) SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J Biol Chem 274:12990–12995PubMedGoogle Scholar
  50. 50.
    Nemoto Y, Kearns BG, Wenk MR et al (2000) Functional characterization of a mammalian Sac1 and mutants exhibiting substrate-specific defects in phosphoinositide phosphatase activity. J Biol Chem 275:34293–34305PubMedGoogle Scholar
  51. 51.
    Rivas MP, Kearns BG, Xie Z et al (1999) Pleiotropic alterations in lipid metabolism in yeast sac1 mutants: relationship to “bypass Sec14p” and inositol auxotrophy. Mol Biol Cell 10:2235–2250PubMedGoogle Scholar
  52. 52.
    Tahirovic S, Schorr M, Mayinger P (2005) Regulation of intracellular phosphatidylinositol-4-phosphate by the Sac1 lipid phosphatase. Traffic 6:116–130PubMedGoogle Scholar
  53. 53.
    Zhong S, Hsu F, Stefan CJ et al (2012) Allosteric activation of the phosphoinositide phosphatase Sac1 by anionic phospholipids. Biochemistry 51:3170–3177PubMedGoogle Scholar
  54. 54.
    Honda A, Nogami M, Yokozeki T et al (1999) Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation. Cell 99:521–532PubMedGoogle Scholar
  55. 55.
    Roth MG (2004) Phosphoinositides in constitutive membrane traffic. Physiol Rev 84:699–730PubMedGoogle Scholar
  56. 56.
    Stephens LR, Jackson TR, Hawkins PT (1993) Agonist-stimulated synthesis of phosphatidylinositol(3,4,5)-trisphosphate: a new intracellular signalling system? Biochim Biophys Acta 1179:27–75PubMedGoogle Scholar
  57. 57.
    Myers MP, Pass I, Batty IH et al (1998) The lipid phosphatase activity of PTEN is critical for its tumor supressor function. Proc Natl Acad Sci U S A 95:13513–13518PubMedGoogle Scholar
  58. 58.
    Szentpetery Z, Varnai P, Balla T (2010) Acute manipulation of Golgi phosphoinositides to assess their importance in cellular trafficking and signaling. Proc Natl Acad Sci U S A 107:8225–8230PubMedGoogle Scholar
  59. 59.
    Dowler S, Currie RA, Campbell DG et al (2000) Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities. Biochem J 351:19–31Google Scholar
  60. 60.
    Ngo M, Ridgway ND (2009) Oxysterol binding protein–related protein 9 (ORP9) is a cholesterol transfer protein that regulates Golgi structure and function. Mol Biol Cell 20:1388–1399Google Scholar
  61. 61.
    Ragaz C, Pietsch H, Urwyler S et al (2008) The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cell Microbiol 10:2416–2433Google Scholar
  62. 62.
    Wang J, Sun HQ, Macia E et al (2007) PI4P promotes the recruitment of the GGA adaptor proteins to the trans-Golgi network and regulates their recognition of the ubiquitin sorting signal. Mol Biol Cell 18:2646–2655PubMedGoogle Scholar
  63. 63.
    Wood CS, Schmitz KR, Bessman NJ et al (2009) PtdIns4P recognition by Vps74/GOLPH3 links PtdIns 4-kinase signaling to retrograde Golgi trafficking. J Cell Biol 187:967–975PubMedGoogle Scholar
  64. 64.
    Zhou Y, Li S, Mäyränpää MI et al (2010) OSBP-related protein 11 (ORP11) dimerizes with ORP9 and localizes at the Golgi–late endosome interface. Exp Cell Res 316:3304–3316PubMedGoogle Scholar
  65. 65.
    Cao X, Coskun U, Rossle M et al (2009) Golgi protein FAPP2 tubulates membranes. Proc Natl Acad Sci U S A 106(50):21121–21125PubMedGoogle Scholar
  66. 66.
    Godi A, Di Campli A, Konstantakopoulos A et al (2004) FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nat Cell Biol 6:393–404PubMedGoogle Scholar
  67. 67.
    He J, Scott JL, Heroux A et al (2011) Molecular basis of phosphatidylinositol 4-phosphate and ARF1 GTPase recognition by the FAPP1 pleckstrin homology (PH) domain. J Biol Chem 286:18650–18657PubMedGoogle Scholar
  68. 68.
    Lenoir M, Coskun U, Grzybek M et al (2010) Structural basis of wedging the Golgi membrane by FAPP pleckstrin homology domains. EMBO Rep 11:279–284PubMedGoogle Scholar
  69. 69.
    Hirst J, Motley A, Harasaki K et al (2003) EpsinR: an ENTH domain-containing protein that interacts with AP-1. Mol Biol Cell 14:625–641PubMedGoogle Scholar
  70. 70.
    Levine TP, Munro S (2002) Targeting of Golgi-specific pleckstrin homology domains involves both PtdIns 4-kinase-dependent and -independent components. Curr Biol 12:695–704PubMedGoogle Scholar
  71. 71.
    Sugiki T, Takeuchi K, Yamaji T et al (2012) Structural basis for the Golgi-association by the pleckstrin homology domain of the ceramide trafficking protein CERT. J Biol Chem 287(40):33706–33718PubMedGoogle Scholar
  72. 72.
    Levine TP, Munro S (1998) The pleckstrin homology domain of oxysterol-binding protein recognises a determinant specific to Golgi membranes. Curr Biol 8:729–739PubMedGoogle Scholar
  73. 73.
    Dippold HC, Ng MM, Farber-Katz SE et al (2009) GOLPH3 bridges phosphatidylinositol-4- phosphate and actomyosin to stretch and shape the Golgi to promote budding. Cell 139:337–351PubMedGoogle Scholar
  74. 74.
    Stahelin RV, Karathanassis D, Murray D et al (2007) Structural and membrane binding analysis of the Phox homology domain of Bem1p: basis of phosphatidylinositol 4-phosphate specificity. J Biol Chem 282:25737–25747PubMedGoogle Scholar
  75. 75.
    Wild AC, Yu JW, Lemmon MA et al (2004) The p21-activated protein kinase-related kinase Cla4 is a coincidence detector of signaling by Cdc42 and phosphatidylinositol 4-phosphate. J Biol Chem 279:17101–17110PubMedGoogle Scholar
  76. 76.
    Natarajan P, Liu K, Patil DV et al (2009) Regulation of a Golgi flippase by phosphoinositides and an ArfGEF. Nat Cell Biol 11:1421–1426PubMedGoogle Scholar
  77. 77.
    Demmel L, Gravert M, Ercan E et al (2008) The clathrin adaptor Gga2p is a phosphatidylinositol 4-phosphate effector at the Golgi exit. Mol Biol Cell 19:1991–2002PubMedGoogle Scholar
  78. 78.
    Levine TP, Munro S (2001) Dual targeting of Osh1p, a yeast homologue of oxysterol-binding protein, to both the Golgi and the nucleus-vacuole junction. Mol Biol Cell 12:1633–1644PubMedGoogle Scholar
  79. 79.
    Li X, Rivas MP, Fang M et al (2002) Analysis of oxysterol binding protein homologue Kes1p function in regulation of Sec14p-dependent protein transport from the yeast Golgi complex. J Cell Biol 157:63–77PubMedGoogle Scholar
  80. 80.
    de Saint-Jean M, Delfosse V, Douguet D et al (2011) Osh4p exchanges sterols for phosphatidylinositol 4-phosphate between lipid bilayers. J Cell Biol 195:965–978PubMedGoogle Scholar
  81. 81.
    Yamashita S, Oku M, Wasada Y et al (2006) PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy. J Cell Biol 173:709–717PubMedGoogle Scholar
  82. 82.
    Mizuno-Yamasaki E, Medkova M, Coleman J et al (2010) Phosphatidylinositol 4-phosphate controls both membrane recruitment and a regulatory switch of the Rab GEF Sec2p. Dev Cell 18:828–840PubMedGoogle Scholar
  83. 83.
    Weber SS, Ragaz C, Reus K et al (2006) Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS Pathog 2:e46PubMedGoogle Scholar
  84. 84.
    Brombacher E, Urwyler S, Ragaz C et al (2009) Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila. J Biol Chem 284:4846–4856PubMedGoogle Scholar
  85. 85.
    Tuzi S, Uekama N, Okada M et al (2003) Structure and dynamics of the phospholipase C-delta1 pleckstrin homology domain located at the lipid bilayer surface. J Biol Chem 278:28019–28025PubMedGoogle Scholar
  86. 86.
    Duncan MC, Payne GS (2003) ENTH/ANTH domains expand to the Golgi. Trends Cell Biol 13:211–215PubMedGoogle Scholar
  87. 87.
    Daboussi L, Costaguta G, Payne GS (2012) Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network. Nat Cell Biol 14:239–248PubMedGoogle Scholar
  88. 88.
    Heldwein EE, Macia E, Wang J et al (2004) Crystal structure of the clathrin adaptor protein 1 core. Proc Natl Acad Sci U S A 101:14108–14113PubMedGoogle Scholar
  89. 89.
    Miller SE, Collins BM, McCoy AJ et al (2007) A SNARE-adaptor interaction is a new mode of cargo recognition in clathrin-coated vesicles. Nature 450:570–574PubMedGoogle Scholar
  90. 90.
    Schmitz KR, Liu J, Li S et al (2008) Golgi localization of glycosyltransferases requires a Vps74p oligomer. Dev Cell 14:523–534PubMedGoogle Scholar
  91. 91.
    Schoebel S, Blankenfeldt W, Goody RS et al (2010) High-affinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA. EMBO Rep 11:598–604PubMedGoogle Scholar
  92. 92.
    Truschel ST, Sengupta D, Foote A et al (2011) Structure of the membrane-tethering GRASP domain reveals a unique PDZ ligand interaction that mediates Golgi biogenesis. J Biol Chem 286:20125–20129PubMedGoogle Scholar
  93. 93.
    Collins BM, McCoy AJ, Kent HM et al (2002) Molecular architecture and functional model of the endocytic AP2 complex. Cell 109:523–535PubMedGoogle Scholar
  94. 94.
    Crottet P, Meyer DM, Rohrer J et al (2002) ARF1.GTP, tyrosine-based signals, and phosphatidylinositol 4,5-bisphosphate constitute a minimal machinery to recruit the AP-1 clathrin adaptor to membranes. Mol Biol Cell 13:3672–3682PubMedGoogle Scholar
  95. 95.
    Mills IG, Praefcke GJ, Vallis Y et al (2003) EpsinR: an AP1/clathrin interacting protein involved in vesicle trafficking. J Cell Biol 160:213–222PubMedGoogle Scholar
  96. 96.
    Horvath CA, Vanden Broeck D, Boulet GA et al (2007) Epsin: inducing membrane curvature. Int J Biochem Cell Biol 39:1765–1770PubMedGoogle Scholar
  97. 97.
    Hirst J, Miller SE, Taylor MJ et al (2004) EpsinR is an adaptor for the SNARE protein Vti1b. Mol Biol Cell 15:5593–5602PubMedGoogle Scholar
  98. 98.
    Doray B, Ghosh P, Griffith J et al (2002) Cooperation of GGAs and AP-1 in packaging MPRs at the trans-Golgi network. Science 297:1700–1703PubMedGoogle Scholar
  99. 99.
    Kato Y, Misra S, Puertollano R et al (2002) Phosphoregulation of sorting signal-VHS domain interactions by a direct electrostatic mechanism. Nat Struct Mol Biol 9:532–536Google Scholar
  100. 100.
    Misra S, Puertollano R, Kato Y et al (2002) Structural basis for acidic-cluster-dileucine sorting-signal recognition by VHS domains. Nature 415:933–937PubMedGoogle Scholar
  101. 101.
    Puertollano R, Aguilar RC, Gorshkova I et al (2001) Sorting of mannose 6-phosphate receptors mediated by the GGAs. Science 292:1712–1716PubMedGoogle Scholar
  102. 102.
    Shiba T, Kawasaki M, Takatsu H et al (2003) Molecular mechanism of membrane recruitment of GGA by ARF in lysosomal protein transport. Nat Struct Biol 10:386–393PubMedGoogle Scholar
  103. 103.
    Takatsu H, Katoh Y, Shiba Y et al (2001) Golgi-localizing, γ-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains. J Biol Chem 276:28541–28545PubMedGoogle Scholar
  104. 104.
    Takatsu H, Yoshino K, Toda K et al (2002) GGA proteins associate with Golgi membranes through interaction between their GGAH domains and ADP-ribosylation factors. Biochem J 365:369–378PubMedGoogle Scholar
  105. 105.
    Kawasaki M, Shiba T, Shiba Y et al (2005) Molecular mechanism of ubiquitin recognition by GGA3 GAT domain. Genes Cells 10:639–654PubMedGoogle Scholar
  106. 106.
    Wahle T, Prager K, Raffler N et al (2005) GGA proteins regulate retrograde transport of BACE1 from endosomes to the trans-Golgi network. Mol Cell Neurosci 29:453–461PubMedGoogle Scholar
  107. 107.
    Puertollano R, van der Wel NN, Greene LE et al (2003) Morphology and dynamics of clathrin/GGA1-coated carriers budding from the trans-Golgi network. Mol Biol Cell 14:1545–1557PubMedGoogle Scholar
  108. 108.
    Hirst J, Lui WW, Bright NA et al (2000) A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome. J Cell Biol 149:67–80PubMedGoogle Scholar
  109. 109.
    Hirst J, Lindsay MR, Robinson MS (2001) GGAs: roles of the different domains and comparison with AP-1 and clathrin. Mol Biol Cell 12:3573–3588PubMedGoogle Scholar
  110. 110.
    Barr FA, Puype M, Vandekerckhove J et al (1997) GRASP65, a protein involved in the stacking of Golgi cisternae. Cell 91:253–262PubMedGoogle Scholar
  111. 111.
    Shorter J, Watson R, Giannakou ME et al (1999) GRASP55, a second mammalian GRASP protein involved in the stacking of Golgi cisternae in a cell-free system. EMBO J 18:4949–4960PubMedGoogle Scholar
  112. 112.
    Puthenveedu MA, Bachert C, Puri S et al (2006) GM130 and GRASP65-dependent lateral cisternal fusion allows uniform Golgi-enzyme distribution. Nat Cell Biol 8:238–248PubMedGoogle Scholar
  113. 113.
    Kuo A, Zhong C, Lane WS et al (2000) Transmembrane transforming growth factor-alpha tethers to the PDZ domain-containing, Golgi membrane-associated protein p59/GRASP55. EMBO J 19:6427–6439PubMedGoogle Scholar
  114. 114.
    Short B, Preisinger C, Korner R et al (2001) A GRASP55-rab2 effector complex linking Golgi structure to membrane traffic. J Cell Biol 155:877–883PubMedGoogle Scholar
  115. 115.
    Waters MG, Pfeffer SR (1999) Membrane tethering in intracellular transport. Curr Opin Cell Biol 11:453–459PubMedGoogle Scholar
  116. 116.
    Orci L, Perrelet A, Rothman JE (1998) Vesicles on strings: morphological evidence for processive transport within the Golgi stack. Proc Natl Acad Sci U S A 95:2279–2283PubMedGoogle Scholar
  117. 117.
    Tu L, Tai WCS, Chen L et al (2008) Signal-mediated dynamic retention of glycosyltransferases in the Golgi. Science 321:404–407PubMedGoogle Scholar
  118. 118.
    Snyder CM, Mardones GA, Ladinsky MS et al (2006) GMx33 associates with the trans-Golgi matrix in a dynamic manner and sorts within tubules exiting the Golgi. Mol Biol Cell 17:511–524PubMedGoogle Scholar
  119. 119.
    Wu CC, Taylor RS, Lane DR et al (2000) GMx33: a novel family of trans-Golgi proteins identified by proteomics. Traffic 1:963–975PubMedGoogle Scholar
  120. 120.
    Bishe B, Syed GH, Field SJ et al (2012) Role of phosphatidylinositol 4-phosphate (PI4P) and its binding protein GOLPH3 in hepatitis C virus secretion. J Biol Chem 287:27637–27647PubMedGoogle Scholar
  121. 121.
    Isberg RR, O’Connor TJ, Heidtman M (2009) The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat Rev Microbiol 7:13–24PubMedGoogle Scholar
  122. 122.
    Machner MP, Isberg RR (2007) A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science 318:974–977PubMedGoogle Scholar
  123. 123.
    Schoebel S, Oesterlin LK, Blankenfeldt W et al (2009) RabGDI displacement by DrrA from Legionella is a consequence of its guanine nucleotide exchange activity. Mol Cell 36:1060–1072PubMedGoogle Scholar
  124. 124.
    Suh H-Y, Lee D-W, Lee K-H et al (2010) Structural insights into the dual nucleotide exchange and GDI displacement activity of SidM/DrrA. EMBO J 29:496–504PubMedGoogle Scholar
  125. 125.
    Müller MP, Peters H, Blümer J et al (2010) The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science 329:946–949PubMedGoogle Scholar
  126. 126.
    Fugmann T, Hausser A, Schoffler P et al (2007) Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein. J Cell Biol 178:15–22PubMedGoogle Scholar
  127. 127.
    Hanada K (2006) Discovery of the molecular machinery CERT for endoplasmic reticulum-to-Golgi trafficking of ceramide. Mol Cell Biochem 286:23–31PubMedGoogle Scholar
  128. 128.
    Hanada K, Kumagai K, Yasuda S et al (2003) Molecular machinery for non-vesicular trafficking of ceramide. Nature 426:803–809PubMedGoogle Scholar
  129. 129.
    Kawano M, Kumagai K, Nishijima M et al (2006) Efficient trafficking of ceramide from the endoplasmic reticulum to the Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif of CERT. J Biol Chem 281:30279–30288PubMedGoogle Scholar
  130. 130.
    Kudo N, Kumagai K, Tomishige N et al (2008) Structural basis for specific lipid recognition by CERT responsible for nonvesicular trafficking of ceramide. Proc Natl Acad Sci U S A 105:488–493PubMedGoogle Scholar
  131. 131.
    Nhek S, Ngo M, Yang X et al (2010) Regulation of oxysterol-binding protein Golgi localization through protein kinase D-mediated phosphorylation. Mol Biol Cell 21:2327–2337PubMedGoogle Scholar
  132. 132.
    Perry RJ, Ridgway ND (2006) Oxysterol-binding protein and vesicle-associated membrane protein-associated protein are required for sterol-dependent activation of the ceramide transport protein. Mol Biol Cell 17:2604–2616PubMedGoogle Scholar
  133. 133.
    Furuita K, Jee J, Fukada H et al (2010) Electrostatic interaction between oxysterol-binding protein and VAMP-associated protein A revealed by NMR and mutagenesis studies. J Biol Chem 285:12961–12970PubMedGoogle Scholar
  134. 134.
    D’Angelo G, Polishchuk E, Di Tullio G et al (2007) Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature 449:62–67PubMedGoogle Scholar
  135. 135.
    Vieira OV, Verkade P, Manninen A et al (2005) FAPP2 is involved in the transport of apical cargo in polarized MDCK cells. J Cell Biol 170:521–526PubMedGoogle Scholar
  136. 136.
    Blomberg N, Baraldi E, Nilges M et al (1999) The PH superfold: a structural scaffold for multiple functions. Trends Biochem Sci 24:441–445PubMedGoogle Scholar
  137. 137.
    Moravcevic K, Oxley CL, Lemmon MA (2012) Conditional peripheral membrane proteins: facing up to limited specificity. Structure 20:15–27PubMedGoogle Scholar
  138. 138.
    Iglesias T, Rozengurt E (1998) Protein kinase D activation by mutations within its pleckstrin homology domain. J Biol Chem 273:410–416PubMedGoogle Scholar
  139. 139.
    Lemmon MA (2004) Pleckstrin homology domains: not just for phosphoinositides. Biochem Soc Trans 32:707–711PubMedGoogle Scholar
  140. 140.
    Rameh LE, Arvidsson A, Carraway KL 3rd et al (1997) A comparative analysis of the phosphoinositide binding specificity of pleckstrin homology domains. J Biol Chem 272:22059–22066PubMedGoogle Scholar
  141. 141.
    Ridgway ND, Dawson PA, Ho YK et al (1992) Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. J Cell Biol 116:307–319PubMedGoogle Scholar
  142. 142.
    Olkkonen VM, Johansson M, Suchanek M et al (2006) The OSBP-related proteins (ORPs): global sterol sensors for co-ordination of cellular lipid metabolism, membrane trafficking and signalling processes? Biochem Soc Trans 34:389–391PubMedGoogle Scholar
  143. 143.
    Mikitova V, Levine TP (2012) Analysis of the key elements of FFAT-like motifs identifies new proteins that potentially bind VAP on the ER, including two AKAPs and FAPP2. PLoS One 7:e30455PubMedGoogle Scholar
  144. 144.
    Huitema K, van den Dikkenberg J, Brouwers JF et al (2004) Identification of a family of animal sphingomyelin synthases. EMBO J 23:33–44PubMedGoogle Scholar
  145. 145.
    Toth B, Balla A, Ma H et al (2006) Phosphatidylinositol 4-kinase IIIbeta regulates the transport of ceramide between the endoplasmic reticulum and Golgi. J Biol Chem 281:36369–36377PubMedGoogle Scholar
  146. 146.
    Kumagai K, Kawano M, Shinkai-Ouchi F et al (2007) Interorganelle trafficking of ceramide is regulated by phosphorylation-dependent cooperativity between the PH and START domains of CERT. J Biol Chem 282:17758–17766PubMedGoogle Scholar
  147. 147.
    Saito S, Matsui H, Kawano M et al (2008) Protein phosphatase 2Cepsilon is an endoplasmic reticulum integral membrane protein that dephosphorylates the ceramide transport protein CERT to enhance its association with organelle membranes. J Biol Chem 283:6584–6593PubMedGoogle Scholar
  148. 148.
    Amako Y, Syed GH, Siddiqui A (2011) Protein kinase D negatively regulates hepatitis C virus secretion through phosphorylation of oxysterol-binding protein and ceramide transfer protein. J Biol Chem 286:11265–11274PubMedGoogle Scholar
  149. 149.
    Wang PY, Weng J, Lee S et al (2008) The N terminus controls sterol binding while the C terminus regulates the scaffolding function of OSBP. J Biol Chem 283:8034–8045PubMedGoogle Scholar
  150. 150.
    Peretti D, Dahan N, Shimoni E et al (2008) Coordinated lipid transfer between the endoplasmic reticulum and the Golgi complex requires the VAP proteins and is essential for Golgi-mediated transport. Mol Biol Cell 19:3871–3884PubMedGoogle Scholar
  151. 151.
    Wang PY, Weng J, Anderson RG (2005) OSBP is a cholesterol-regulated scaffolding protein in control of ERK 1/2 activation. Science 307:1472–1476PubMedGoogle Scholar
  152. 152.
    Lagace TA, Byers DM, Cook HW et al (1997) Altered regulation of cholesterol and cholesteryl ester synthesis in Chinese-hamster ovary cells overexpressing the oxysterol-binding protein is dependent on the pleckstrin homology domain. Biochem J 326(Pt 1):205–213PubMedGoogle Scholar
  153. 153.
    Mohammadi A, Perry RJ, Storey MK et al (2001) Golgi localization and phosphorylation of oxysterol binding protein in Niemann-Pick C and U18666A-treated cells. J Lipid Res 42:1062–1071PubMedGoogle Scholar
  154. 154.
    Storey MK, Byers DM, Cook HW et al (1998) Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol. Biochem J 336(Pt 1):247–256PubMedGoogle Scholar
  155. 155.
    Perry RJ, Ridgway ND (2005) Molecular mechanisms and regulation of ceramide transport. Biochim Biophys Acta 1734:220–234PubMedGoogle Scholar
  156. 156.
    Wyles JP, McMaster CR, Ridgway ND (2002) Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum. J Biol Chem 277:29908–29918PubMedGoogle Scholar
  157. 157.
    Lessmann E, Ngo M, Leitges M et al (2007) Oxysterol-binding protein-related protein (ORP) 9 is a PDK-2 substrate and regulates Akt phosphorylation. Cell Signal 19:384–392PubMedGoogle Scholar
  158. 158.
    Weixel KM, Blumental-Perry A, Watkins SC et al (2005) Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases. J Biol Chem 280:10501–10508PubMedGoogle Scholar
  159. 159.
    Vermeer JEM, Thole JM, Goedhart J et al (2009) Imaging phosphatidylinositol 4-phosphate dynamics in living plant cells. Plant J 57:356–372PubMedGoogle Scholar
  160. 160.
    Halter D, Neumann S, van Dijk SM et al (2007) Pre- and post-Golgi translocation of glucosylceramide in glycosphingolipid synthesis. J Cell Biol 179:101–115PubMedGoogle Scholar
  161. 161.
    Baron CL, Malhotra V (2002) Role of diacylglycerol in PKD recruitment to the TGN and protein transport to the plasma membrane. Science 295:325–328PubMedGoogle Scholar
  162. 162.
    Pusapati GV, Krndija D, Armacki M et al (2010) Role of the second cysteine-rich domain and Pro275 in protein kinase D2 interaction with ADP-ribosylation factor 1, trans-Golgi network recruitment, and protein transport. Mol Biol Cell 21:1011–1022PubMedGoogle Scholar
  163. 163.
    Diaz Anel AM, Malhotra V (2005) PKCeta is required for beta1gamma2/beta3gamma2- and PKD-mediated transport to the cell surface and the organization of the Golgi apparatus. J Cell Biol 169:83–91PubMedGoogle Scholar
  164. 164.
    Waldron RT, Rozengurt E (2003) Protein kinase C phosphorylates protein kinase D activation loop Ser744 and Ser748 and releases autoinhibition by the pleckstrin homology domain. J Biol Chem 278:154–163PubMedGoogle Scholar
  165. 165.
    Waldron RT, Iglesias T, Rozengurt E (1999) The pleckstrin homology domain of protein kinase D interacts preferentially with the eta isoform of protein kinase C. J Biol Chem 274:9224–9230PubMedGoogle Scholar
  166. 166.
    Oancea E, Bezzerides VJ, Greka A et al (2003) Mechanism of persistent protein kinase D1 translocation and activation. Dev Cell 4:561–574PubMedGoogle Scholar
  167. 167.
    Dascher C, Balch WE (1994) Dominant inhibitory mutants of ARF1 block endoplasmic reticulum to Golgi transport and trigger disassembly of the Golgi apparatus. J Biol Chem 269:1437–1448PubMedGoogle Scholar
  168. 168.
    Dell’Angelica EC, Puertollano R, Mullins C et al (2000) GGAs: a family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex. J Cell Biol 149:81–94PubMedGoogle Scholar
  169. 169.
    Traub LM, Ostrom JA, Kornfeld S (1993) Biochemical dissection of AP-1 recruitment onto Golgi membranes. J Cell Biol 123:561–573PubMedGoogle Scholar
  170. 170.
    Lee I, Doray B, Govero J et al (2008) Binding of cargo sorting signals to AP-1 enhances its association with ADP ribosylation factor 1-GTP. J Cell Biol 180:467–472PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.School of Cancer Sciences, College of Medical and Dental SciencesUniversity of BirminghamEdgbaston, BirminghamUK

Personalised recommendations