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Ca2+ Sensors: Synaptotagmins

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Presynaptic Terminals

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Abstract

Synaptotagmin is a synaptic vesicle membrane protein that is postulated to function as a calcium (Ca2+) sensor for neurotransmitter release. This protein contains two Ca2+-binding domains (C2A, C2B) in its cytoplasmic region. Genetic studies provide strong evidence supporting the idea that synaptotagmin is the Ca2+ sensor for the fast synchronous component of evoked transmitter release. In addition, synaptotagmin appears to be involved in docking and priming (by clamping spontaneous fusion) of synaptic vesicles and regulating fusion pores as well as vesicle endocytosis. In vitro studies demonstrate that synaptotagmin binds to phospholipid membranes in the presence and absence of Ca2+. Furthermore, in response to Ca2+, the tips of synaptotagmin C2 domains penetrate lipid bilayers, altering the membrane curvature. Synaptotagmin also binds to the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex that is believed to be the core fusion machinery, although the findings on the Ca2+ dependency of binding of synaptotagmin to SNARE have been inconsistent and controversial. Taken together, synaptotagmin appears to trigger a fast synchronous component of transmitter release by binding to Ca2+, probably through the interactions with both membranes and SNAREs.

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References

  • Araç D, Chen X, Khant HA, Ubach J, Ludtke SJ, Kikkawa M, Johnson AE, Chiu W, Südhof TC, Rizo J (2006) Close membrane-membrane proximity induced by Ca2+-dependent multivalent binding of synaptotagmin-1 to phospholipids. Nat Struct Mol Biol 13:209–217

    PubMed  Google Scholar 

  • Bacaj T, Wu D, Yang X, Morishita W, Zhou P, Xu W, Malenka RC, Südhof TC (2013) Synaptotagmin-1 and synaptotagmin-7 trigger synchronous and asynchronous phases of neurotransmitter release. Neuron 80:947–959

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bai J, Tucker WC, Chapman ER (2004a) PIP2 increases the speed of response of synaptotagmin and steers its membrane-penetration activity toward the plasma membrane. Nat Struct Mol Biol 11:36–44

    CAS  PubMed  Google Scholar 

  • Bai J, Wang CT, Richards DA, Jackson MB, Chapman ER (2004b) Fusion pore dynamics are regulated by synaptotagmin•t-SNARE interactions. Neuron 41:929–942

    CAS  PubMed  Google Scholar 

  • Bennett MK, Calakos N, Scheller RH (1992) Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones. Science 257:255–259

    CAS  PubMed  Google Scholar 

  • Bommert K, Charlton MP, DeBello WM, Chin GJ, Betz H, Augustine GJ (1993) Inhibition of neurotransmitter release by C2-domain peptides implicates synaptotagmin in exocytosis. Nature 363:163–165

    CAS  PubMed  Google Scholar 

  • Borden CR, Stevens CF, Sullivan JM, Zhu Y (2005) Synaptotagmin mutants Y311N and K326/327A alter the calcium dependence of neurotransmission. Mol Cell Neurosci 29:462–470

    CAS  PubMed  Google Scholar 

  • Bowen ME, Weninger K, Ernst J, Chu S, Brunger AT (2005) Single-molecule studies of synaptotagmin and complexin binding to the SNARE complex. Biophys J 89:690–702

    CAS  PubMed Central  PubMed  Google Scholar 

  • Broadie K, Bellen HJ, DiAntonio A, Littleton JT, Schwarz TL (1994) Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission. Proc Natl Acad Sci USA 91:10727–10731

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brose N, Petrenko AG, Südhof TC, Jahn R (1992) Synaptotagmin: a calcium sensor on the synaptic vesicle surface. Science 256:1021–1025

    CAS  PubMed  Google Scholar 

  • Chapman ER, Davis AF (1998) Direct interaction of a Ca2+-binding loop of synaptotagmin with lipid bilayers. J Biol Chem 273:13995–14001

    CAS  PubMed  Google Scholar 

  • Charvin N, L’Eveque C, Walker D, Berton F, Raymond C, Kataoka M, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ (1997) Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel. EMBO J 16:4591–4596

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng Y, Sequeira SM, Malinina L, Tereshko V, Söllner TH, Patel DJ (2004) Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain. Protein Sci 10:2665–2672

    Google Scholar 

  • Chicka MC, Hui E, Liu H, Chapman ER (2008) Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+. Nat Struct Mol Biol 15:827–835

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chieregatti E, Witkin JW, Baldini G (2002) SNAP-25 and synaptotagmin 1 function in Ca2+-dependent reversible docking of granules to the plasma membrane. Traffic 3:496–511

    CAS  PubMed  Google Scholar 

  • Choi UB, Strop P, Vrljic M, Chu S, Brunger AT, Weninger KR (2010) Single-molecule FRET-derived model of the synaptotagmin 1–SNARE fusion complex. Nat Struct Mol Biol 17:318–324

    CAS  PubMed Central  PubMed  Google Scholar 

  • Connell E, Giniatullina A, Lai-Kee-Him J, Tavare R, Ferrari E, Roseman A, Cojoc D, Brisson AR, Davletov B (2008) Cross-linking of phospholipid membranes is a conserved property of calcium-sensitive synaptotagmins. J Mol Biol 380:42–50

    CAS  PubMed Central  PubMed  Google Scholar 

  • Craxton M (2010) A manual collection of Syt, Esyt, Rph3a, Rph3al, Doc2, and Dblc2 genes from 46 metazoan genomes – an open access resource for neuroscience and evolutionary biology. BMC Genomics 11:37

    PubMed Central  PubMed  Google Scholar 

  • Craxton M, Goedert M (1995) Synaptotagmin V: a novel synaptotagmin isoform expressed in rat brain. FEBS Lett 361:196–200

    CAS  PubMed  Google Scholar 

  • Dai H, Shen N, Araç D, Rizo J (2007) A quaternary SNARE–synaptotagmin–Ca2+–phospholipid complex in neurotransmitter release. J Mol Biol 367:848–863

    CAS  PubMed Central  PubMed  Google Scholar 

  • Davis AF, Bai J, Fasshauer D, Wolowick MJ, Lewis JL, Chapman ER (1999) Kinetics of synaptotagmin responses to Ca2+ and assembly with the core SNARE complex onto membranes. Neuron 24:363–376

    CAS  PubMed  Google Scholar 

  • Davletov BA, Südhof TC (1993) A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding. J Biol Chem 268:26386–26390

    CAS  PubMed  Google Scholar 

  • de Wit H, Walter AM, Milosevic I, Gulyas-Kovacs A, Riedel D, Sørensen JB, Verhage M (2009) Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes. Cell 138:935–946

    PubMed  Google Scholar 

  • DeBello WM, Betz H, Augustine GJ (1993) Synaptotagmin and neurotransmitter release. Cell 74:947–950

    CAS  PubMed  Google Scholar 

  • Desai RC, Vyas B, Earles CA, Littleton JT, Kowalchyck JA, Martin TF, Chapman ER (2000) The C2B domain of synaptotagmin is a Ca2+-sensing module essential for exocytosis. J Cell Biol 150:1125–1136

    CAS  PubMed Central  PubMed  Google Scholar 

  • DiAntonio A, Schwarz TL (1994) The effect on synaptic physiology of synaptotagmin mutations in Drosophila. Neuron 12:909–920

    CAS  PubMed  Google Scholar 

  • DiAntonio A, Parfitt KD, Schwarz TL (1993) Synaptic transmission persists in synaptotagmin mutants of Drosophila. Cell 73:1281–1290

    CAS  PubMed  Google Scholar 

  • Earles CA, Bai J, Wang P, Chapman ER (2001) The tandem C2 domains of synaptotagmin contain redundant Ca2+ binding sites that cooperate to engage t-SNAREs and trigger exocytosis. J Cell Biol 154:1117–1123

    CAS  PubMed Central  PubMed  Google Scholar 

  • Elferink LA, Peterson MR, Scheller RH (1993) A role for synaptotagmin (p65) in regulated exocytosis. Cell 72:153–159

    CAS  PubMed  Google Scholar 

  • Ernst JA, Brunger AT (2003) High resolution structure, stability, and synaptotagmin binding of a truncated neuronal SNARE complex. J Biol Chem 278:8630–8636

    CAS  PubMed  Google Scholar 

  • Fernandez I, Araç D, Ubach J, Gerber SH, Shin O, Gao Y, Anderson RG, Südhof TC, Rizo J (2001) Three-dimensional structure of the synaptotagmin 1 C2B-domain: synaptotagmin 1 as a phospholipid binding machine. Neuron 32:1057–1069

    CAS  PubMed  Google Scholar 

  • Fernández-Chacón R, Königstorfer A, Gerber SH, Garcia J, Matos MF, Stevens CF, Brose N, Rizo J, Rosenmund C, Südhof TC (2001) Synaptotagmin I functions as a calcium regulator of release probability. Nature 410:41–49

    PubMed  Google Scholar 

  • Fox MA, Sanes JR (2007) Synaptotagmin I and II are present in distinct subsets of central synapses. J Comp Neurol 503:280–296

    CAS  PubMed  Google Scholar 

  • Fukuda M (2003) Molecular cloning, expression, and characterization of a novel class of synaptotagmin (Syt XIV) conserved from Drosophila to humans. J Biochem 133:641–649

    CAS  PubMed  Google Scholar 

  • Fukuda M, Aruga J, Niinobe M, Aimoto S, Mikoshiba K (1994) Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II. J Biol Chem 269:29206–29211

    CAS  PubMed  Google Scholar 

  • Fukuda M, Moreira JE, Lewis FM, Sugimori M, Niinobe M, Mikoshiba K, Llinás R (1995) Role of the C2B domain of synaptotagmin in vesicular release and recycling as determined by specific antibody injection into the squid giant synapse preterminal. Proc Natl Acad Sci USA 92:10708–10712

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fukuda M, Moreira JE, Liu V, Sugimori M, Mikoshiba K, Llinas RR (2000) Role of the conserved WHXL motif in the C terminus of synaptotagmin in synaptic vesicle docking. Proc Natl Acad Sci USA 97:14715–14719

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fuson KL, Montes M, Robert JJ, Sutton RB (2007) Structure of human synaptotagmin 1 C2AB in the absence of Ca2+ reveals a novel domain association. Biochemistry 46:13041–13048

    CAS  PubMed  Google Scholar 

  • Geppert M, Archer BT III, Südhof TC (1991) Synaptotagmin II. A novel differentially distributed form of synaptotagmin. J Biol Chem 266:13548–13552

    CAS  PubMed  Google Scholar 

  • Geppert M, Goda Y, Hammer RE, Li C, Rosahl TW, Stevens CF, Südhof TC (1994) Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell 79:717–727

    CAS  PubMed  Google Scholar 

  • Gerona RR, Larsen EC, Kowalchyk JA, Martin TF (2000) The C terminus of SNAP25 is essential for Ca2+-dependent binding of synaptotagmin to SNARE complexes. J Biol Chem 275:6328–6336

    CAS  PubMed  Google Scholar 

  • Giraudo CG, Eng WS, Melia TJ, Rothman JE (2006) A clamping mechanism involved in SNARE-dependent exocytosis. Science 313:676–680

    CAS  PubMed  Google Scholar 

  • Goda Y, Stevens CF (1994) Two components of transmitter release at a central synapse. Proc Natl Acad Sci USA 91:12942–12946

    CAS  PubMed Central  PubMed  Google Scholar 

  • Herrick DZ, Sterbling S, Rasch KA, Hinderliter A, Cafiso DS (2006) Position of synaptotagmin I at the membrane interface: cooperative interactions of tandem C2 domains. Biochemistry 45:9668–9674

    CAS  PubMed  Google Scholar 

  • Herrick DZ, Kuo W, Huang H, Schwieters CD, Ellena JF, Cafiso DS (2009) Solution and membrane-bound conformations of the tandem C2A and C2B domains of synaptotagmin 1: evidence for bilayer bridging. J Mol Biol 390:913–923

    CAS  PubMed Central  PubMed  Google Scholar 

  • Holt M, Riedel D, Stein A, Schuette C, Jahn R (2008) Synaptic vesicles are constitutively active fusion machines that function independently of Ca2+. Curr Biol 18:715–722

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hu K, Carroll J, Fedorovich S, Rickman C, Sukhodub A, Davletov B (2002) Vesicular restriction of synaptobrevin suggests a role for calcium in membrane fusion. Nature 415:646–650

    CAS  PubMed  Google Scholar 

  • Hudson AW, Birnbaum MJ (1995) Identification of a nonneuronal isoform of synaptotagmin. Proc Natl Acad Sci USA 92:5895–5899

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hui E, Bai J, Chapman ER (2006) Ca2+-triggered simultaneous membrane penetration of the tandem C2-domains of synaptotagmin I. Biophys J 91:1767–1777

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hui E, Johnson CP, Yao J, Dunning FM, Chapman ER (2009) Synaptotagmin-mediated bending of the target membrane is a critical step in Ca2+-regulated fusion. Cell 138:709–721

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hui E, Gaffaney JD, Wang Z, Johnson CP, Evans CS, Chapman ER (2011) Mechanism and function of synaptotagmin-mediated membrane apposition. Nat Struct Mol Biol 18:813–821

    CAS  PubMed Central  PubMed  Google Scholar 

  • Iezzi M, Eliasson L, Fukuda M, Wollheim CB (2005) Adenovirus-mediated silencing of synaptotagmin 9 inhibits Ca2+-dependent insulin secretion in islets. FEBS Lett 579:5241–5246

    CAS  PubMed  Google Scholar 

  • Jorgensen EM, Hartwieg E, Schuske K, Nonet ML, Jin Y, Horvitz HR (1995) Defective recycling of synaptic vesicles in synaptotagmin mutants of Caenorhabditis elegans. Nature 378:196–199

    CAS  PubMed  Google Scholar 

  • Joung M-J, Mohan SK, Yu C (2012) Molecular level interaction of inositol hexaphosphate with the C2B domain of human synaptotagmin I. Biochemistry 51:3675–3683

    CAS  PubMed  Google Scholar 

  • Kee Y, Scheller RH (1996) Localization of synaptotagmin-binding domains on syntaxin. J Neurosci 16:1975–1981

    CAS  PubMed  Google Scholar 

  • Kerr AM, Reisinger E, Jonas P (2008) Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses. Proc Natl Acad Sci USA 105:15581–15586

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim JY, Choi BK, Choi MG, Kim SA, Lai Y, Shin YK, Lee NK (2012) Solution single-vesicle assay reveals PIP2-mediated sequential actions of synaptotagmin-1 on SNAREs. EMBO J 31:2144–2155

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kochubey O, Schneggenburger R (2011) Synaptotagmin increases the dynamic range of synapses by driving Ca2+-evoked release and by clamping a near-linear remaining Ca2+ sensor. Neuron 69:736–748

    CAS  PubMed  Google Scholar 

  • Krishnakumar SS, Radoff DT, Kummel D, Giraudo CG, Li F, Khandan L, Baguley SW, Coleman J, Reinisch KM, Pincet F, Rothman JE (2011) A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion. Nat Struct Mol Biol 18:934–940

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kyoung M, Srivastava A, Zhang Y, Diao J, Vrljic M, Grob P, Nogales E, Chu S, Brunger AT (2011) In vitro system capable of differentiating fast Ca2+-triggered content mixing from lipid exchange for mechanistic studies of neurotransmitter release. Proc Natl Acad Sci USA 108:E304–E313

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lai AL, Huang H, Herrick DZ, Epp N, Cafiso DS (2011) Synaptotagmin 1 and SNAREs form a complex that is structurally heterogeneous. J Mol Biol 405:696–706

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lai Y, Diao J, Liu Y, Ishitsuka Y, Su Z, Schulten K, Ha T, Shin Y-K (2013) Fusion pore formation and expansion induced by Ca2+ and synaptotagmin 1. Proc Natl Acad Sci USA 110:1333–1338

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee HK, Yang Y, Su Z, Hyeon C, Lee TS, Lee HW, Kweon DH, Shin YK, Yoon TY (2010) Dynamic Ca2+-dependent stimulation of vesicle fusion by membrane-anchored synaptotagmin 1. Science 328:760–763

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee J, Guan Z, Akbergenova Y, Littleton JT (2013) Genetic analysis of synaptotagmin C2 domain specificity in regulating spontaneous and evoked neurotransmitter release. J Neurosci 33:187–200

    CAS  PubMed Central  PubMed  Google Scholar 

  • Leveque C, Hoshino T, David P, Shoji-Kasai Y, Leys K, Omori A, Lang B, el Far O, Sato K, Martin-Moutot N, Newsom-Davis J, Takahashi M, Seagar MJ (1992) The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen. Proc Natl Acad Sci USA 89:3625–3629

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lévêque C, el Far O, Martin-Moutot N, Sato K, Kato R, Takahashi M, Seagar MJ (1994) Purification of the N-type calcium channel associated with syntaxin and synaptotagmin. A complex implicated in synaptic vesicle exocytosis. J Biol Chem 269:6306–6312

    PubMed  Google Scholar 

  • Leveque C, Boudier JA, Takahashi M, Seagar M (2000) Calcium-dependent dissociation of synaptotagmin from synaptic SNARE complexes. J Neurochem 74:367–374

    CAS  PubMed  Google Scholar 

  • Li C, Ullrich B, Zhang JZ, Anderson RG, Brose N, Südhof TC (1995) Ca2+-dependent and -independent activities of neural and non-neural synaptotagmins. Nature 375:594–599

    CAS  PubMed  Google Scholar 

  • Li L, Shin OH, Rhee JS, Araç D, Rah JC, Rizo J, Südhof T, Rosenmund C (2006) Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1. J Biol Chem 281:15845–15852

    CAS  PubMed  Google Scholar 

  • Littleton JT, Stern M, Schulze K, Perin M, Bellen HJ (1993) Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca2+-activated neurotransmitter release. Cell 74:1125–1134

    CAS  PubMed  Google Scholar 

  • Littleton JT, Stern M, Perin M, Bellen HJ (1994) Calcium dependence of neurotransmitter release and rate of spontaneous vesicle fusions are altered in Drosophila synaptotagmin mutants. Proc Natl Acad Sci USA 91:10888–10892

    CAS  PubMed Central  PubMed  Google Scholar 

  • Littleton JT, Bai J, Vyas B, Desai R, Baltus AE, Garment MB, Carlson SD, Ganetzky B, Chapman ER (2001) Synaptotagmin mutants reveal essential functions for the C2B domain in Ca2+-triggered fusion and recycling of synaptic vesicles in vivo. J Neurosci 21:1421–1433

    CAS  PubMed  Google Scholar 

  • Llinás R, Sugimori M, Lang EJ, Morita M, Fukuda M, Niinobe M, Mikoshiba K (1994) The inositol high-polyphosphate series blocks synaptic transmission by preventing vesicular fusion: a squid giant synapse study. Proc Natl Acad Sci USA 91:12990–12993

    PubMed Central  PubMed  Google Scholar 

  • Loewen CA, Lee SM, Shin YK, Reist NE (2006) C2B polylysine motif of synaptotagmin facilitates a Ca2+-independent stage of synaptic vesicle priming in vivo. Mol Biol Cell 17:5211–5226

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lynch KL, Martin TF (2007) Synaptotagmins I and IX function redundantly in regulated exocytosis but not endocytosis in PC12 cells. J Cell Sci 120:617–627

    CAS  PubMed  Google Scholar 

  • Lynch KL, Gerona RR, Larsen EC, Marcia RF, Mitchell JC, Martin TF (2007) Synaptotagmin C2A loop 2 mediates Ca2+-dependent SNARE interactions essential for Ca2+-triggered vesicle exocytosis. Mol Biol Cell 18:4957–4968

    CAS  PubMed Central  PubMed  Google Scholar 

  • Mace KE, Biela LM, Sares AG, Reist NE (2009) Synaptotagmin I stabilizes synaptic vesicles via its C2A polylysine motif. Genesis 47:337–345

    CAS  PubMed  Google Scholar 

  • Mackler JM, Reist NE (2001) Mutations in the second C2 domain of synaptotagmin disrupt synaptic transmission at Drosophila neuromuscular junctions. J Comp Neurol 436:4–16

    CAS  PubMed  Google Scholar 

  • Mackler JM, Drummond JA, Loewen CA, Robinson IM, Reist NE (2002) The C2B Ca2+-binding motif of synaptotagmin is required for synaptic transmission in vivo. Nature 418:340–344

    CAS  PubMed  Google Scholar 

  • Mahal LK, Sequeira SM, Gureasko JM, Söllner TH (2002) Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I. J Cell Biol 158:273–282

    CAS  PubMed Central  PubMed  Google Scholar 

  • Marquèze B, Boudier JA, Mizuta M, Inagaki N, Seino S, Seagar M (1995) Cellular localization of synaptotagmin I, II, and III mRNAs in the central nervous system and pituitary and adrenal glands of the rat. J Neurosci 15:4906–4917

    PubMed  Google Scholar 

  • Martens S, Kozlov MM, McMahon HT (2007) How synaptotagmin promotes membrane fusion. Science 316:1205–1208

    CAS  PubMed  Google Scholar 

  • Martina JA, Bonangelino CJ, Aguilar RC, Bonifacino JS (2001) Stonin 2: an adaptor-like protein that interacts with components of the endocytic machinery. J Cell Biol 153:1111–1120

    CAS  PubMed Central  PubMed  Google Scholar 

  • Masumoto T, Suzuki K, Ohmori I, Michiue H, Tomizawa K, Fujimura A, Nishiki T, Matsui H (2012) Ca2+-independent syntaxin binding to the C2B effector region of synaptotagmin. Mol Cell Neurosci 49:1–8

    CAS  PubMed  Google Scholar 

  • Matsuoka H, Harada K, Nakamura J, Fukuda M, Inoue M (2011) Differential distribution of synaptotagmin-1, -4, -7, and -9 in rat adrenal chromaffin cells. Cell Tissue Res 344:41–50

    PubMed  Google Scholar 

  • Matthew WD, Tsavaler L, Reichardt LF (1981) Identification of a synaptic vesicle-specific membrane protein with a wide distribution in neuronal and neurosecretory tissue. J Cell Biol 91:257–269

    CAS  PubMed  Google Scholar 

  • Mehrotra B, Elliott JT, Chen J, Olszewski JD, Profit AA, Chaudhary A, Fukuda M, Mikoshiba K, Prestwich GD (1997) Selective photoaffinity labeling of the inositol polyphosphate binding C2B domains of synaptotagmins. J Biol Chem 272:4237–4244

    CAS  PubMed  Google Scholar 

  • Mikoshiba K, Fukuda M, Ibata K, Kabayama H, Mizutani A (1999) Role of synaptotagmin, a Ca2+ and inositol polyphosphate binding protein, in neurotransmitter release and neurite outgrowth. Chem Phys Lipids 98:59–67

    CAS  PubMed  Google Scholar 

  • Mittelsteadt T, Seifert G, Alvarez-Baron E, Steinhauser C, Becker AJ, Schoch S (2009) Differential mRNA expression patterns of the synaptotagmin gene family in the rodent brain. J Comp Neurol 512:514–528

    CAS  PubMed  Google Scholar 

  • Mizutani A, Fukuda M, Niinobe M, Mikoshiba K (1997) Regulation of AP-2-synaptotagmin interaction by inositol high polyphosphates. Biochem Biophys Res Commun 240:128–131

    CAS  PubMed  Google Scholar 

  • Mochida S, Fukuda M, Niinobe M, Kobayashi H, Mikoshiba K (1997) Roles of synaptotagmin C2 domains in neurotransmitter secretion and inositol high-polyphosphate binding at mammalian cholinergic synapses. Neuroscience 77:937–943

    CAS  PubMed  Google Scholar 

  • Mohrmann R, de Wit H, Connell E, Pinheiro PS, Leese C, Bruns D, Davletov B, Verhage M, Sørensen JB (2013) Synaptotagmin interaction with SNAP-25 governs vesicle docking, priming, and fusion triggering. J Neurosci 33:14417–14430

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morimoto T, Popov S, Buckley KM, Poo MM (1995) Calcium-dependent transmitter secretion from fibroblasts: modulation by synaptotagmin I. Neuron 15:689–696

    CAS  PubMed  Google Scholar 

  • Nagy G, Kim JH, Pang ZP, Matti U, Rettig J, Südhof TC, Sørensen JB (2006) Different effects on fast exocytosis induced by synaptotagmin 1 and 2 isoforms and abundance but not by phosphorylation. J Neurosci 26:632–643

    CAS  PubMed  Google Scholar 

  • Nicholson-Tomishima K, Ryan TA (2004) Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I. Proc Natl Acad Sci USA 101:16648–16652

    CAS  PubMed Central  PubMed  Google Scholar 

  • Niinobe M, Yamaguchi Y, Fukuda M, Mikoshiba K (1994) Synaptotagmin is an inositol polyphosphate binding protein: isolation and characterization as an Ins 1,3,4,5-P4 binding protein. Biochem Biophys Res Commun 205:1036–1042

    CAS  PubMed  Google Scholar 

  • Nishiki T, Augustine GJ (2004a) Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons. J Neurosci 24:6127–6132

    PubMed  Google Scholar 

  • Nishiki T, Augustine GJ (2004b) Dual roles of the C2B domain of synaptotagmin I in synchronizing Ca2+-dependent neurotransmitter release. J Neurosci 24:8542–8550

    CAS  PubMed  Google Scholar 

  • Nishizuka Y (1988) The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334:661–665

    CAS  PubMed  Google Scholar 

  • Nonet ML, Grundahl K, Meyer BJ, Rand JB (1993) Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin. Cell 73:1291–1305

    CAS  PubMed  Google Scholar 

  • Ohara-Imaizumi M, Fukuda M, Niinobe M, Misonou H, Ikeda K, Murakami T, Kawasaki M, Mikoshiba K, Kumakura K (1997) Distinct roles of C2A and C2B domains of synaptotagmin in the regulation of exocytosis in adrenal chromaffin cells. Proc Natl Acad Sci USA 94:287–291

    CAS  PubMed Central  PubMed  Google Scholar 

  • Osborne SL, Herreros J, Bastiaens PI, Schiavo G (1999) 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 274:59–66

    CAS  PubMed  Google Scholar 

  • Paddock BE, Wang Z, Biela LM, Chen K, Getzy MD, Striegel A, Richmond JE, Chapman ER, Featherstone DE, Reist NE (2011) Membrane penetration by synaptotagmin is required for coupling calcium binding to vesicle fusion in vivo. J Neurosci 31:2248–2257

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pang ZP, Melicoff E, Padgett D, Liu Y, Teich AF, Dickey BF, Lin W, Adachi R, Südhof TC (2006a) Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses. J Neurosci 26:13493–13504

    CAS  PubMed  Google Scholar 

  • Pang ZP, Sun J, Rizo J, Maximov A, Südhof TC (2006b) Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release. EMBO J 25:2039–2050

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park Y, Hernandez JM, van den Bogaart G, Ahmed S, Holt M, Riedel D, Jahn R (2012) Controlling synaptotagmin activity by electrostatic screening. Nat Struct Mol Biol 19:991–997

    CAS  PubMed Central  PubMed  Google Scholar 

  • Perin MS, Fried VA, Mignery GA, Jahn R, Südhof TC (1990) Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C. Nature 345:260–263

    CAS  PubMed  Google Scholar 

  • Perin MS, Brose N, Jahn R, Südhof TC (1991) Domain structure of synaptotagmin (p65). J Biol Chem 266:623–629

    CAS  PubMed  Google Scholar 

  • Popov SV, Poo MM (1993) Synaptotagmin: a calcium-sensitive inhibitor of exocytosis? Cell 73:1247–1249

    CAS  PubMed  Google Scholar 

  • Poskanzer KE, Marek KW, Sweeney ST, Davis GW (2003) Synaptotagmin I is necessary for compensatory synaptic vesicle endocytosis in vivo. Nature 426:559–563

    CAS  PubMed  Google Scholar 

  • Radhakrishnan A, Stein A, Jahn R, Fasshauer D (2009) The Ca2+ affinity of synaptotagmin 1 is markedly increased by a specific interaction of its C2B domain with phosphatidylinositol 4,5-bisphosphate. J Biol Chem 284:25749–25760

    CAS  PubMed Central  PubMed  Google Scholar 

  • Reist NE, Buchanan J, Li J, DiAntonio A, Buxton EM, Schwarz TL (1998) Morphologically docked synaptic vesicles are reduced in synaptotagmin mutants of Drosophila. J Neurosci 18:7662–7673

    CAS  PubMed  Google Scholar 

  • Rhee JS, Li LY, Shin OH, Rah JC, Rizo J, Südhof TC, Rosenmund C (2005) Augmenting neurotransmitter release by enhancing the apparent Ca2+ affinity of synaptotagmin 1. Proc Natl Acad Sci USA 102:18664–18669

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rickman C, Davletov B (2003) Mechanism of calcium-independent synaptotagmin binding to target SNAREs. J Biol Chem 278:5501–5504

    CAS  PubMed  Google Scholar 

  • Rickman C, Archer DA, Meunier FA, Craxton M, Fukuda M, Burgoyne RD, Davletov B (2004) Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate. J Biol Chem 279:12574–12579

    CAS  PubMed  Google Scholar 

  • Rickman C, Jiménez JL, Graham ME, Archer DA, Soloviev M, Burgoyne RD, Davletov B (2006) Conserved prefusion protein assembly in regulated exocytosis. Mol Biol Cell 17:283–294

    CAS  PubMed Central  PubMed  Google Scholar 

  • Robinson IM, Ranjan R, Schwarz TL (2002) Synaptotagmins I and IV promote transmitter release independently of Ca2+ binding in the C2A domain. Nature 418:336–340

    CAS  PubMed  Google Scholar 

  • Sabatini BL, Regehr WG (1996) Timing of neurotransmission at fast synapses in the mammalian brain. Nature 384:170–172

    CAS  PubMed  Google Scholar 

  • Schiavo G, Gu QM, Prestwich GD, Söllner TH, Rothman JE (1996) Calcium-dependent switching of the specificity of phosphoinositide binding to synaptotagmin. Proc Natl Acad Sci USA 93:13327–13332

    CAS  PubMed Central  PubMed  Google Scholar 

  • Seven AB, Brewer KD, Shi L, Jiang Q-X, Rizo J (2013) Prevalent mechanism of membrane bridging by synaptotagmin-1. Proc Natl Acad Sci USA 110:E3243–E3252

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shahin V, Datta D, Hui E, Henderson RM, Chapman ER, Edwardson JM (2008) Synaptotagmin perturbs the structure of phospholipid bilayers. Biochemistry 47:2143–2152

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shao X, Davletov BA, Sutton RB, Südhof TC, Rizo J (1996) Bipartite Ca2+-binding motif in C2 domains of synaptotagmin and protein kinase C. Science 273:248–251

    CAS  PubMed  Google Scholar 

  • Shao X, Li C, Fernandez I, Zhang X, Südhof TC, Rizo J (1997) Synaptotagmin-syntaxin interaction: the C2 domain as a Ca2+-dependent electrostatic switch. Neuron 18:133–142

    CAS  PubMed  Google Scholar 

  • Shao X, Fernandez I, Südhof TC, Rizo J (1998) Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change? Biochemistry 37:16106–16115

    CAS  PubMed  Google Scholar 

  • Sheng ZH, Yokoyama CT, Catterall WA (1997) Interaction of the synprint site of N-type Ca2+ channels with the C2B domain of synaptotagmin I. Proc Natl Acad Sci USA 94:5405–5410

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shin OH, Rhee JS, Tang J, Sugita S, Rosenmund C, Südhof TC (2003) Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. Neuron 37:99–108

    CAS  PubMed  Google Scholar 

  • Shin OH, Xu J, Rizo J, Südhof TC (2009) Differential but convergent functions of Ca2+ binding to synaptotagmin-1 C2 domains mediate neurotransmitter release. Proc Natl Acad Sci USA 106:16469–16474

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shoji-Kasai Y, Yoshida A, Sato K, Hoshino T, Ogura A, Kondo S, Fujimoto Y, Kuwahara R, Kato R, Takahashi M (1992) Neurotransmitter release from synaptotagmin-deficient clonal variants of PC12 cells. Science 256:1821–1823

    CAS  PubMed  Google Scholar 

  • Söllner T, Bennett MK, Whiteheart SW, Scheller RH, Rothman JE (1993) A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion. Cell 75:409–418

    PubMed  Google Scholar 

  • Sørensen JB, Matti U, Wei SH, Nehring RB, Voets T, Ashery U, Binz T, Neher E, Rettig J (2002) The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis. Proc Natl Acad Sci USA 99:1627–1632

    PubMed Central  PubMed  Google Scholar 

  • Stein A, Radhakrishnan A, Riedel D, Fasshauer D, Jahn R (2007) Synaptotagmin activates membrane fusion through a Ca2+-dependent trans interaction with phospholipids. Nat Struct Mol Biol 14:904–911

    CAS  PubMed  Google Scholar 

  • Stevens CF, Sullivan JM (2003) The synaptotagmin C2A domain is part of the calcium sensor controlling fast synaptic transmission. Neuron 39:299–308

    CAS  PubMed  Google Scholar 

  • Striegel AR, Biela LM, Evans CS, Wang Z, Delehoy JB, Sutton RB, Chapman ER, Reist NE (2012) Calcium binding by synaptotagmin’s C2A domain is an essential element of the electrostatic switch that triggers synchronous synaptic transmission. J Neurosci 32:1253–1260

    CAS  PubMed Central  PubMed  Google Scholar 

  • Südhof TC, Rothman JE (2009) Membrane fusion: grappling with SNARE and SM proteins. Science 323:474–477

    PubMed Central  PubMed  Google Scholar 

  • Sun J, Pang ZP, Qin D, Fahim AT, Adachi R, Südhof TC (2007) A dual-Ca2+-sensor model for neurotransmitter release in a central synapse. Nature 450:676–682

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sutton RB, Davletov BA, Berghuis AM, Südhof TC, Sprang SR (1995) Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold. Cell 80:929–938

    CAS  PubMed  Google Scholar 

  • Sutton RB, Ernst JA, Brunger AT (1999) Crystal structure of the cytosolic C2A-C2B domains of synaptotagmin III. Implications for Ca+2-independent snare complex interaction. J Cell Biol 147:589–598

    CAS  PubMed Central  PubMed  Google Scholar 

  • Takahashi M, Arimatsu Y, Fujita S, Fujimoto Y, Kondo S, Hama T, Miyamoto E (1991) Protein kinase C and Ca2+/calmodulin-dependent protein kinase II phosphorylate a novel 58-kDa protein in synaptic vesicles. Brain Res 551:279–292

    CAS  PubMed  Google Scholar 

  • Takamori S, Holt M, Stenius K, Lemke EA, Grønborg M, Riedel D, Urlaub H, Schenck S, Brügger B, Ringler P, Müller SA, Rammner B, Gräter F, Hub JS, De Groot BL, Mieskes G, Moriyama Y, Klingauf J, Grubmüller H, Heuser J, Wieland F, Jahn R (2006) Molecular anatomy of a trafficking organelle. Cell 127:831–846

    CAS  PubMed  Google Scholar 

  • Tang J, Maximov A, Shin OH, Dai H, Rizo J, Südhof TC (2006) A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell 126:1175–1187

    CAS  PubMed  Google Scholar 

  • Tokumaru H, Shimizu-Okabe C, Abe T (2008) Direct interaction of SNARE complex binding protein synaphin/complexin with calcium sensor synaptotagmin 1. Brain Cell Biol 36:173–189

    CAS  PubMed  Google Scholar 

  • Tucker WC, Weber T, Chapman ER (2004) Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs. Science 304:435–438

    CAS  PubMed  Google Scholar 

  • Ubach J, Zhang X, Shao X, Südhof TC, Rizo J (1998) Ca2+ binding to synaptotagmin: how many Ca2+ ions bind to the tip of a C2-domain? EMBO J 17:3921–3930

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ubach J, Lao Y, Fernandez I, Arac D, Südhof TC, Rizo J (2001) The C2B domain of synaptotagmin I is a Ca2+-binding module. Biochemistry 40:5854–5860

    CAS  PubMed  Google Scholar 

  • van den Bogaart G, Thutupalli S, Risselada JH, Meyenberg K, Holt M, Riedel D, Diederichsen U, Herminghaus S, Grubmüller H, Jahn R (2011) Synaptotagmin-1 may be a distance regulator acting upstream of SNARE nucleation. Nat Struct Mol Biol 18:805–812

    PubMed Central  PubMed  Google Scholar 

  • van den Bogaart G, Meyenberg K, Diederichsen U, Jahn R (2012) Phosphatidylinositol 4,5-bisphosphate increases Ca2+ affinity of synaptotagmin-1 by 40-fold. J Biol Chem 287:16447–16453

    PubMed Central  PubMed  Google Scholar 

  • Vennekate W, Schröder S, Lin CC, van den Bogaart G, Grunwald M, Jahn R, Walla PJ (2012) Cis- and trans-membrane interactions of synaptotagmin-1. Proc Natl Acad Sci USA 109:11037–11042

    CAS  PubMed Central  PubMed  Google Scholar 

  • Voets T, Moser T, Lund PE, Chow RH, Geppert M, Südhof TC, Neher E (2001) Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I. Proc Natl Acad Sci USA 98:11680–11685

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vrljic M, Strop P, Hill RC, Hansen KC, Chu S, Brunger AT (2011) Post-translational modifications and lipid binding profile of insect cell-expressed full-length mammalian synaptotagmin 1. Biochemistry 50:9998–10012

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walther K, Krauss M, Diril MK, Lemke S, Ricotta D, Honing S, Kaiser S, Haucke V (2001) Human stoned B interacts with AP-2 and synaptotagmin and facilitates clathrin-coated vesicle uncoating. EMBO Rep 2:634–640

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang CT, Grishanin R, Earles CA, Chang PY, Martin TF, Chapman ER, Jackson MB (2001) Synaptotagmin modulation of fusion pore kinetics in regulated exocytosis of dense-core vesicles. Science 294:1111–1115

    CAS  PubMed  Google Scholar 

  • Wang CT, Lu JC, Bai J, Chang PY, Martin TF, Chapman ER, Jackson MB (2003a) Different domains of synaptotagmin control the choice between kiss-and-run and full fusion. Nature 424:943–947

    CAS  PubMed  Google Scholar 

  • Wang P, Wang CT, Bai J, Jackson MB, Chapman ER (2003b) Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner. J Biol Chem 278:47030–47037

    CAS  PubMed  Google Scholar 

  • Wang CT, Bai J, Chang PY, Chapman ER, Jackson MB (2006) Synaptotagmin-Ca2+ triggers two sequential steps in regulated exocytosis in rat PC12 cells: fusion pore opening and fusion pore dilation. J Physiol 570:295–307

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang Z, Liu H, Gu Y, Chapman ER (2011) Reconstituted synaptotagmin I mediates vesicle docking, priming, and fusion. J Cell Biol 195:1159–1170

    CAS  PubMed Central  PubMed  Google Scholar 

  • Weninger K, Bowen ME, Choi UB, Chu S, Brunger AT (2008) Accessory proteins stabilize the acceptor complex for synaptobrevin, the 1:1 syntaxin/SNAP-25 complex. Structure 16:308–320

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu J, Mashimo T, Südhof TC (2007) Synaptotagmin-1, -2, and -9: Ca2+ sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron 54:567–581

    CAS  PubMed  Google Scholar 

  • Xu J, Pang ZP, Shin OH, Südhof TC (2009) Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nat Neurosci 12:759–766

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu W, Morishita W, Buckmaster PS, Pang ZP, Malenka RC, Südhof TC (2012) Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission. Neuron 73:990–1001

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xue M, Ma C, Craig TK, Rosenmund C, Rizo J (2008) The Janus-faced nature of the C2B domain is fundamental for synaptotagmin-1 function. Nat Struct Mol Biol 15:1160–1168

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang X, Kaeser-Woo YJ, Pang ZP, Xu W, Südhof TC (2010) Complexin clamps asynchronous release by blocking a secondary Ca2+ sensor via its accessory α helix. Neuron 68:907–920

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang SN, Shi Y, Yang G, Li Y, Yu L, Shin O-H, Bacaj T, Südhof TC, Yu J, Berggren P-O (2012) Inositol hexakisphosphate suppresses excitatory neurotransmission via synaptotagmin-1 C2B domain in the hippocampal neuron. Proc Natl Acad Sci USA 109:12183–12188

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao J, Gaffaney JD, Kwon SE, Chapman ER (2011) Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release. Cell 147:666–677

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yao J, Kwon SE, Gaffaney JD, Dunning FM, Chapman ER (2012a) Uncoupling the roles of synaptotagmin I during endo- and exocytosis of synaptic vesicles. Nat Neurosci 15:243–249

    CAS  Google Scholar 

  • Yao LH, Rao Y, Varga K, Wang CY, Xiao P, Lindau M, Gong LW (2012b) Synaptotagmin 1 is necessary for the Ca2+ dependence of clathrin-mediated endocytosis. J Neurosci 32:3778–3785

    CAS  PubMed  Google Scholar 

  • Yoshida A, Oho C, Omori A, Kuwahara R, Ito T, Takahashi M (1992) HPC-1 is associated with synaptotagmin and omega-conotoxin receptor. J Biol Chem 267:24925–24928

    CAS  PubMed  Google Scholar 

  • Yoshihara M, Littleton JT (2002) Synaptotagmin I functions as a calcium sensor to synchronize neurotransmitter release. Neuron 36:897–908

    CAS  PubMed  Google Scholar 

  • Yoshihara M, Guan Z, Littleton JT (2010) Differential regulation of synchronous versus asynchronous neurotransmitter release by the C2 domains of synaptotagmin 1. Proc Natl Acad Sci USA 107:14869–14874

    CAS  PubMed Central  PubMed  Google Scholar 

  • Young SM Jr, Neher E (2009) Synaptotagmin has an essential function in synaptic vesicle positioning for synchronous release in addition to its role as a calcium sensor. Neuron 63:482–496

    CAS  PubMed  Google Scholar 

  • Zhang JZ, Davletov BA, Südhof TC, Anderson RG (1994) Synaptotagmin I is a high affinity receptor for clathrin AP-2: implications for membrane recycling. Cell 78:751–760

    CAS  PubMed  Google Scholar 

  • Zhang X, Kim-Miller MJ, Fukuda M, Kowalchyk JA, Martin TF (2002) Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis. Neuron 34:599–611

    CAS  PubMed  Google Scholar 

  • Zhou A, Brewer KD, Rizo J (2013) Analysis of SNARE complex/synaptotagmin-1 interactions by one-dimensional NMR spectroscopy. Biochemistry 52:3446–3456

    CAS  PubMed  Google Scholar 

  • Zhu D, Zhou W, Liang T, Yang F, Zhang RY, Wu ZX, Xu T (2007) Synaptotagmin I and IX function redundantly in controlling fusion pore of large dense core vesicles. Biochem Biophys Res Commun 361:922–927

    CAS  PubMed  Google Scholar 

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Acknowledgment

This work was supported by JSPS KAKENHI 26460297 to TN. The authors would like to thank Enago (www.enago.jp) for the English language review.

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Authors and Affiliations

  1. Department of Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Tei-ichi Nishiki, Kentaro Kuroki, Toshio Masumoto & Hideki Matsui

  2. Brain Science Institute, RIKEN, Saitama, 351-0198, Japan

    Toshio Masumoto

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  1. Tei-ichi Nishiki
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  2. Kentaro Kuroki
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  3. Toshio Masumoto
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  4. Hideki Matsui
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Correspondence to Tei-ichi Nishiki .

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  1. Department of Physiology, Tokyo Medical University, Tokyo, Japan

    Sumiko Mochida

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Nishiki, Ti., Kuroki, K., Masumoto, T., Matsui, H. (2015). Ca2+ Sensors: Synaptotagmins. In: Mochida, S. (eds) Presynaptic Terminals. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55166-9_8

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