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PMID: 24183019 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Neurotransmitter release: the last millisecond in the life of a synaptic vesicle.

Neuron ·Vol. 80 ·No. 3 ·2013-10-30 ·Pages 675-90

Südhof TC

Abstract

During an action potential, Ca(2+) entering a presynaptic terminal triggers synaptic vesicle exocytosis and neurotransmitter release in less than a millisecond. How does Ca(2+) stimulate release so rapidly and precisely? Work over the last decades revealed that Ca(2+) binding to synaptotagmin triggers release by stimulating synaptotagmin binding to a core fusion machinery composed of SNARE and SM proteins that mediates membrane fusion during exocytosis. Complexin adaptor proteins assist synaptotagmin by activating and clamping this core fusion machinery. Synaptic vesicles containing synaptotagmin are positioned at the active zone, the site of vesicle fusion, by a protein complex containing RIM proteins. RIM proteins activate docking and priming of synaptic vesicles and simultaneously recruit Ca(2+) channels to active zones, thereby connecting in a single complex primed synaptic vesicles to Ca(2+) channels. This architecture allows direct flow of Ca(2+) ions from Ca(2+) channels to synaptotagmin, which then triggers fusion, thus mediating tight millisecond coupling of an action potential to neurotransmitter release.

MeSH Terms
Animals Membrane Fusion Models, Neurological Neurons/physiology Neurotransmitter Agents/metabolism SNARE Proteins/metabolism Synaptic Transmission/physiology Synaptic Vesicles/physiology
Chemicals
Neurotransmitter Agents SNARE Proteins
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Südhof Thomas C
Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Lorry Lokey SIM1 Building, 265 Campus Drive, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: [email protected].
References (146)
146 references, click to expand
  1. CSPα knockout causes neurodegeneration by impairing SNAP-25 function.
    EMBO J. 2012 Feb 15;31(4):829-41 PMID: 22187053
  2. Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons.
    Neuron. 2007 May 24;54(4):567-81 PMID: 17521570
  3. Complexin controls the force transfer from SNARE complexes to membranes in fusion.
    Science. 2009 Jan 23;323(5913):516-21 PMID: 19164751
  4. Complexin controls spontaneous and evoked neurotransmitter release by regulating the timing and properties of synaptotagmin activity.
    J Neurosci. 2012 Dec 12;32(50):18234-45 PMID: 23238737
  5. Ultrahigh-resolution imaging reveals formation of neuronal SNARE/Munc18 complexes in situ.
    Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):E2812-20 PMID: 23821748
  6. Calmodulin and Munc13 form a Ca2+ sensor/effector complex that controls short-term synaptic plasticity.
    Cell. 2004 Aug 6;118(3):389-401 PMID: 15294163
  7. Munc18-1 binding to the neuronal SNARE complex controls synaptic vesicle priming.
    J Cell Biol. 2009 Mar 9;184(5):751-64 PMID: 19255244
  8. Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold.
    Cell. 1995 Mar 24;80(6):929-38 PMID: 7697723
  9. Timing of neurotransmission at fast synapses in the mammalian brain.
    Nature. 1996 Nov 14;384(6605):170-2 PMID: 8906792
  10. A gain-of-function mutation in synaptotagmin-1 reveals a critical role of Ca2+-dependent soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex binding in synaptic exocytosis.
    J Neurosci. 2006 Nov 29;26(48):12556-65 PMID: 17135417
  11. Synaptotagmin-1 and synaptotagmin-7 trigger synchronous and asynchronous phases of neurotransmitter release.
    Neuron. 2013 Nov 20;80(4):947-59 PMID: 24267651
  12. Complexins regulate a late step in Ca2+-dependent neurotransmitter release.
    Cell. 2001 Jan 12;104(1):71-81 PMID: 11163241
  13. Synaptotagmin-7 is a principal Ca2+ sensor for Ca2+ -induced glucagon exocytosis in pancreas.
    J Physiol. 2009 Mar 15;587(Pt 6):1169-78 PMID: 19171650
  14. Alpha-synuclein cooperates with CSPalpha in preventing neurodegeneration.
    Cell. 2005 Nov 4;123(3):383-96 PMID: 16269331
  15. Calmodulin controls synaptic strength via presynaptic activation of calmodulin kinase II.
    J Neurosci. 2010 Mar 17;30(11):4132-42 PMID: 20237283
  16. Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse.
    Cell. 1994 Nov 18;79(4):717-27 PMID: 7954835
  17. Glycosylation and processing of prepro-alpha-factor through the yeast secretory pathway.
    Cell. 1984 Feb;36(2):309-18 PMID: 6420074
  18. A dual-Ca2+-sensor model for neurotransmitter release in a central synapse.
    Nature. 2007 Nov 29;450(7170):676-82 PMID: 18046404
  19. RIM genes differentially contribute to organizing presynaptic release sites.
    Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11830-5 PMID: 22753485
  20. Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory α helix.
    Neuron. 2010 Dec 9;68(5):907-20 PMID: 21145004
  21. Syntaxin: a synaptic protein implicated in docking of synaptic vesicles at presynaptic active zones.
    Science. 1992 Jul 10;257(5067):255-9 PMID: 1321498
  22. Complexin II plays a positive role in Ca2+-triggered exocytosis by facilitating vesicle priming.
    Proc Natl Acad Sci U S A. 2008 Dec 9;105(49):19538-43 PMID: 19033464
  23. A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity?
    EMBO J. 2005 Aug 17;24(16):2839-50 PMID: 16052212
  24. Asynchronous transmitter release from cholecystokinin-containing inhibitory interneurons is widespread and target-cell independent.
    J Neurosci. 2009 Sep 9;29(36):11112-22 PMID: 19741117
  25. Synaptic vesicle fusion.
    Nat Struct Mol Biol. 2008 Jul;15(7):665-74 PMID: 18618940
  26. Single-molecule studies of the neuronal SNARE fusion machinery.
    Annu Rev Biochem. 2009;78:903-28 PMID: 19489736
  27. Direct interactions between C. elegans RAB-3 and Rim provide a mechanism to target vesicles to the presynaptic density.
    Neurosci Lett. 2008 Oct 24;444(2):137-42 PMID: 18721860
  28. How Tlg2p/syntaxin 16 'snares' Vps45.
    EMBO J. 2002 Jul 15;21(14):3620-31 PMID: 12110575
  29. Regulation of transmitter release by Ca(2+) and synaptotagmin: insights from a large CNS synapse.
    Trends Neurosci. 2011 May;34(5):237-46 PMID: 21439657
  30. Complexin maintains vesicles in the primed state in C. elegans.
    Curr Biol. 2011 Jan 25;21(2):106-13 PMID: 21215631
  31. The C(2)B Ca(2+)-binding motif of synaptotagmin is required for synaptic transmission in vivo.
    Nature. 2002 Jul 18;418(6895):340-4 PMID: 12110842
  32. A conformational switch in syntaxin during exocytosis: role of munc18.
    EMBO J. 1999 Aug 16;18(16):4372-82 PMID: 10449403
  33. The ROP-syntaxin interaction inhibits neurotransmitter release.
    Eur J Cell Biol. 2001 Feb;80(2):196-9 PMID: 11302525
  34. Synaptotagmin-2 controls regulated exocytosis but not other secretory responses of mast cells.
    J Biol Chem. 2009 Jul 17;284(29):19445-51 PMID: 19473977
  35. Mice sans synaptotagmin.
    Nature. 1994 Nov 24;372(6504):316-7 PMID: 7969483
  36. Synaptotagmin I functions as a calcium sensor to synchronize neurotransmitter release.
    Neuron. 2002 Dec 5;36(5):897-908 PMID: 12467593
  37. Synaptotagmin VII is targeted to dense-core vesicles and regulates their Ca2+ -dependent exocytosis in PC12 cells.
    J Biol Chem. 2004 Dec 10;279(50):52677-84 PMID: 15456748
  38. Alternative zippering as an on-off switch for SNARE-mediated fusion.
    Science. 2009 Jan 23;323(5913):512-6 PMID: 19164750
  39. One SNARE complex is sufficient for membrane fusion.
    Nat Struct Mol Biol. 2010 Mar;17(3):358-64 PMID: 20139985
  40. Synaptotagmin I functions as a calcium regulator of release probability.
    Nature. 2001 Mar 1;410(6824):41-9 PMID: 11242035
  41. v-SNARE actions during Ca(2+)-triggered exocytosis.
    Cell. 2007 Oct 19;131(2):351-63 PMID: 17956735
  42. A complexin fusion clamp regulates spontaneous neurotransmitter release and synaptic growth.
    Nat Neurosci. 2007 Oct;10(10):1235-7 PMID: 17873870
  43. Selective activation of cognate SNAREpins by Sec1/Munc18 proteins.
    Cell. 2007 Jan 12;128(1):183-95 PMID: 17218264
  44. Silence of Synaptotagmin VII inhibits release of dense core vesicles in PC12 cells.
    Sci China C Life Sci. 2009 Dec;52(12):1156-63 PMID: 20016973
  45. Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice.
    J Cell Biol. 2003 Aug 18;162(4):543-9 PMID: 12925704
  46. Structural basis for a Munc13-1 homodimer to Munc13-1/RIM heterodimer switch.
    PLoS Biol. 2006 Jul;4(7):e192 PMID: 16732694
  47. SNARE force synchronizes synaptic vesicle fusion and controls the kinetics of quantal synaptic transmission.
    J Neurosci. 2010 Aug 4;30(31):10272-81 PMID: 20685972
  48. Complexin has opposite effects on two modes of synaptic vesicle fusion.
    Curr Biol. 2011 Jan 25;21(2):97-105 PMID: 21215634
  49. The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1627-32 PMID: 11830673
  50. Synaptic cross talk between perisomatic-targeting interneuron classes expressing cholecystokinin and parvalbumin in hippocampus.
    J Neurosci. 2009 Apr 1;29(13):4140-54 PMID: 19339609
  51. The RIM/NIM family of neuronal C2 domain proteins. Interactions with Rab3 and a new class of Src homology 3 domain proteins.
    J Biol Chem. 2000 Jun 30;275(26):20033-44 PMID: 10748113
  52. Synaptic transmission persists in synaptotagmin mutants of Drosophila.
    Cell. 1993 Jul 2;73(7):1281-90 PMID: 8100740
  53. Structural and functional conservation of synaptotagmin (p65) in Drosophila and humans.
    J Biol Chem. 1991 Jan 5;266(1):615-22 PMID: 1840599
  54. Complexins: cytosolic proteins that regulate SNAP receptor function.
    Cell. 1995 Oct 6;83(1):111-9 PMID: 7553862
  55. Fast vesicle fusion in living cells requires at least three SNARE complexes.
    Science. 2010 Oct 22;330(6003):502-5 PMID: 20847232
  56. Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin.
    Nature. 1993 Nov 25;366(6453):347-51 PMID: 8247129
  57. Two synaptobrevin molecules are sufficient for vesicle fusion in central nervous system synapses.
    Proc Natl Acad Sci U S A. 2011 Aug 23;108(34):14318-23 PMID: 21844343
  58. Munc18-1 binds directly to the neuronal SNARE complex.
    Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2697-702 PMID: 17301226
  59. Rim is a putative Rab3 effector in regulating synaptic-vesicle fusion.
    Nature. 1997 Aug 7;388(6642):593-8 PMID: 9252191
  60. Synaptotagmins form a hierarchy of exocytotic Ca(2+) sensors with distinct Ca(2+) affinities.
    EMBO J. 2002 Feb 1;21(3):270-80 PMID: 11823420
  61. Lipid-anchored SNAREs lacking transmembrane regions fully support membrane fusion during neurotransmitter release.
    Neuron. 2013 Oct 16;80(2):470-83 PMID: 24120845
  62. Autonomous function of synaptotagmin 1 in triggering synchronous release independent of asynchronous release.
    Neuron. 2005 Nov 23;48(4):547-54 PMID: 16301172
  63. Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10.
    Cell. 2011 Apr 15;145(2):300-11 PMID: 21496647
  64. Syntaxin-1 N-peptide and Habc-domain perform distinct essential functions in synaptic vesicle fusion.
    EMBO J. 2013 Jan 9;32(1):159-71 PMID: 23188083
  65. The fine structure of neurons.
    J Biophys Biochem Cytol. 1955 Jan;1(1):69-88 PMID: 14381429
  66. A protein assembly-disassembly pathway in vitro that may correspond to sequential steps of synaptic vesicle docking, activation, and fusion.
    Cell. 1993 Nov 5;75(3):409-18 PMID: 8221884
  67. SNARE requirements en route to exocytosis: from many to few.
    J Mol Neurosci. 2012 Oct;48(2):387-94 PMID: 22427188
  68. Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming.
    Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):9037-42 PMID: 12070347
  69. Synaptotagmin-2 is essential for survival and contributes to Ca2+ triggering of neurotransmitter release in central and neuromuscular synapses.
    J Neurosci. 2006 Dec 27;26(52):13493-504 PMID: 17192432
  70. Resolving the function of distinct Munc18-1/SNARE protein interaction modes in a reconstituted membrane fusion assay.
    J Biol Chem. 2011 Sep 2;286(35):30582-30590 PMID: 21730064
  71. Reconstitution of the vital functions of Munc18 and Munc13 in neurotransmitter release.
    Science. 2013 Jan 25;339(6118):421-5 PMID: 23258414
  72. Nanodomain coupling between Ca²⁺ channels and sensors of exocytosis at fast mammalian synapses.
    Nat Rev Neurosci. 2011 Dec 20;13(1):7-21 PMID: 22183436
  73. Synaptotagmin increases the dynamic range of synapses by driving Ca²+-evoked release and by clamping a near-linear remaining Ca²+ sensor.
    Neuron. 2011 Feb 24;69(4):736-48 PMID: 21338883
  74. Complexin activates exocytosis of distinct secretory vesicles controlled by different synaptotagmins.
    J Neurosci. 2013 Jan 23;33(4):1714-27 PMID: 23345244
  75. Mutational analysis of Drosophila synaptotagmin demonstrates its essential role in Ca(2+)-activated neurotransmitter release.
    Cell. 1993 Sep 24;74(6):1125-34 PMID: 8104705
  76. Sec1p binds to SNARE complexes and concentrates at sites of secretion.
    J Cell Biol. 1999 Jul 26;146(2):333-44 PMID: 10427089
  77. Distinct kinetic changes in neurotransmitter release after SNARE protein cleavage.
    Science. 2005 Jul 15;309(5733):491-4 PMID: 16020741
  78. Sec18p (NSF)-driven release of Sec17p (alpha-SNAP) can precede docking and fusion of yeast vacuoles.
    Cell. 1996 Apr 5;85(1):83-94 PMID: 8620540
  79. CSPα promotes SNARE-complex assembly by chaperoning SNAP-25 during synaptic activity.
    Nat Cell Biol. 2011 Jan;13(1):30-9 PMID: 21151134
  80. Synaptotagmin function in dense core vesicle exocytosis studied in cracked PC12 cells.
    Nat Neurosci. 2002 Jul;5(7):649-56 PMID: 12055633
  81. Structural determinants of synaptobrevin 2 function in synaptic vesicle fusion.
    J Neurosci. 2006 Jun 21;26(25):6668-76 PMID: 16793874
  82. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro.
    Science. 2010 Sep 24;329(5999):1663-7 PMID: 20798282
  83. A single C2 domain from synaptotagmin I is sufficient for high affinity Ca2+/phospholipid binding.
    J Biol Chem. 1993 Dec 15;268(35):26386-90 PMID: 8253763
  84. Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+.
    J Gen Physiol. 2003 Sep;122(3):265-76 PMID: 12939392
  85. Co-operative action a calcium ions in transmitter release at the neuromuscular junction.
    J Physiol. 1967 Nov;193(2):419-32 PMID: 6065887
  86. Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice.
    Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3992-7 PMID: 18308938
  87. Membrane fusion: grappling with SNARE and SM proteins.
    Science. 2009 Jan 23;323(5913):474-7 PMID: 19164740
  88. Single-Vesicle Fusion Assay Reveals Munc18-1 Binding to the SNARE Core Is Sufficient for Stimulating Membrane Fusion.
    ACS Chem Neurosci. 2010 Mar 17;1(3):168-174 PMID: 20300453
  89. Multiple kinetic components of exocytosis distinguished by neurotoxin sensitivity.
    Nat Neurosci. 1998 Jul;1(3):192-200 PMID: 10195143
  90. C-terminal complexin sequence is selectively required for clamping and priming but not for Ca2+ triggering of synaptic exocytosis.
    J Neurosci. 2012 Feb 22;32(8):2877-85 PMID: 22357870
  91. Dual modes of Munc18-1/SNARE interactions are coupled by functionally critical binding to syntaxin-1 N terminus.
    J Neurosci. 2007 Nov 7;27(45):12147-55 PMID: 17989281
  92. Doc2 supports spontaneous synaptic transmission by a Ca(2+)-independent mechanism.
    Neuron. 2011 Apr 28;70(2):244-51 PMID: 21521611
  93. Distinct domains of complexin I differentially regulate neurotransmitter release.
    Nat Struct Mol Biol. 2007 Oct;14(10):949-58 PMID: 17828276
  94. Genetic analysis of synaptotagmin C2 domain specificity in regulating spontaneous and evoked neurotransmitter release.
    J Neurosci. 2013 Jan 2;33(1):187-200 PMID: 23283333
  95. RIM-binding protein, a central part of the active zone, is essential for neurotransmitter release.
    Science. 2011 Dec 16;334(6062):1565-9 PMID: 22174254
  96. Subtle Interplay between synaptotagmin and complexin binding to the SNARE complex.
    J Mol Biol. 2013 Sep 23;425(18):3461-75 PMID: 23845424
  97. Absence of synaptotagmin disrupts excitation-secretion coupling during synaptic transmission.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10727-31 PMID: 7938019
  98. Syntaxin N-terminal peptide motif is an initiation factor for the assembly of the SNARE-Sec1/Munc18 membrane fusion complex.
    Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22399-406 PMID: 21139055
  99. Augmenting neurotransmitter release by enhancing the apparent Ca2+ affinity of synaptotagmin 1.
    Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18664-9 PMID: 16352718
  100. Dual roles of the C2B domain of synaptotagmin I in synchronizing Ca2+-dependent neurotransmitter release.
    J Neurosci. 2004 Sep 29;24(39):8542-50 PMID: 15456828
  101. Push-and-pull regulation of the fusion pore by synaptotagmin-7.
    Proc Natl Acad Sci U S A. 2010 Nov 2;107(44):19032-7 PMID: 20956309
  102. Differential but convergent functions of Ca2+ binding to synaptotagmin-1 C2 domains mediate neurotransmitter release.
    Proc Natl Acad Sci U S A. 2009 Sep 22;106(38):16469-74 PMID: 19805322
  103. Synaptotagmin: a calcium sensor on the synaptic vesicle surface.
    Science. 1992 May 15;256(5059):1021-5 PMID: 1589771
  104. Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins.
    Nature. 1995 Jun 15;375(6532):594-9 PMID: 7791877
  105. Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human.
    Biochem J. 2002 Jul 1;365(Pt 1):173-80 PMID: 12071850
  106. Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis.
    Neuron. 2002 May 16;34(4):599-611 PMID: 12062043
  107. Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2-domain proteins.
    J Biol Chem. 1995 Oct 20;270(42):25273-80 PMID: 7559667
  108. A clamping mechanism involved in SNARE-dependent exocytosis.
    Science. 2006 Aug 4;313(5787):676-80 PMID: 16794037
  109. Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release.
    Nat Neurosci. 2009 Jun;12(6):759-66 PMID: 19412166
  110. Ordering the final events in yeast exocytosis.
    J Cell Biol. 2000 Oct 16;151(2):439-52 PMID: 11038189
  111. Synaptotagmin-1 and -7 are functionally overlapping Ca2+ sensors for exocytosis in adrenal chromaffin cells.
    Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3998-4003 PMID: 18308932
  112. Model systems for membrane fusion.
    Chem Soc Rev. 2011 Mar;40(3):1572-85 PMID: 21152599
  113. Molecular anatomy of a trafficking organelle.
    Cell. 2006 Nov 17;127(4):831-46 PMID: 17110340
  114. De novo mutations in the gene encoding STXBP1 (MUNC18-1) cause early infantile epileptic encephalopathy.
    Nat Genet. 2008 Jun;40(6):782-8 PMID: 18469812
  115. Neuroligins and neurexins link synaptic function to cognitive disease.
    Nature. 2008 Oct 16;455(7215):903-11 PMID: 18923512
  116. Mutations in the second C2 domain of synaptotagmin disrupt synaptic transmission at Drosophila neuromuscular junctions.
    J Comp Neurol. 2001 Jul 16;436(1):4-16 PMID: 11413542
  117. C2 domains of protein kinase C isoforms alpha, beta, and gamma: activation parameters and calcium stoichiometries of the membrane-bound state.
    Biochemistry. 2002 Sep 24;41(38):11411-24 PMID: 12234184
  118. Molecular machines governing exocytosis of synaptic vesicles.
    Nature. 2012 Oct 11;490(7419):201-7 PMID: 23060190
  119. Asynchronous GABA release generates long-lasting inhibition at a hippocampal interneuron-principal neuron synapse.
    Nat Neurosci. 2005 Oct;8(10):1319-28 PMID: 16158066
  120. Beta phorbol ester- and diacylglycerol-induced augmentation of transmitter release is mediated by Munc13s and not by PKCs.
    Cell. 2002 Jan 11;108(1):121-33 PMID: 11792326
  121. Unraveling the mechanisms of synaptotagmin and SNARE function in neurotransmitter release.
    Trends Cell Biol. 2006 Jul;16(7):339-50 PMID: 16698267
  122. Munc13-1 is essential for fusion competence of glutamatergic synaptic vesicles.
    Nature. 1999 Jul 29;400(6743):457-61 PMID: 10440375
  123. SNAP receptors implicated in vesicle targeting and fusion.
    Nature. 1993 Mar 25;362(6418):318-24 PMID: 8455717
  124. Sly1 binds to Golgi and ER syntaxins via a conserved N-terminal peptide motif.
    Dev Cell. 2002 Mar;2(3):295-305 PMID: 11879635
  125. RIM proteins activate vesicle priming by reversing autoinhibitory homodimerization of Munc13.
    Neuron. 2011 Jan 27;69(2):317-31 PMID: 21262469
  126. A molecular machine for neurotransmitter release: synaptotagmin and beyond.
    Nat Med. 2013 Oct;19(10):1227-31 PMID: 24100992
  127. Complexins facilitate neurotransmitter release at excitatory and inhibitory synapses in mammalian central nervous system.
    Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7875-80 PMID: 18505837
  128. Synaptotagmin VII as a plasma membrane Ca(2+) sensor in exocytosis.
    Neuron. 2001 May;30(2):459-73 PMID: 11395007
  129. Synaptotagmin VII modulates the kinetics of dense-core vesicle exocytosis in PC12 cells.
    Genes Cells. 2007 Apr;12(4):511-9 PMID: 17397398
  130. A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis.
    Cell. 2006 Sep 22;126(6):1175-87 PMID: 16990140
  131. RIM determines Ca²+ channel density and vesicle docking at the presynaptic active zone.
    Neuron. 2011 Jan 27;69(2):304-16 PMID: 21262468
  132. SNARE proteins: one to fuse and three to keep the nascent fusion pore open.
    Science. 2012 Mar 16;335(6074):1355-9 PMID: 22422984
  133. Distinct neuronal coding schemes in memory revealed by selective erasure of fast synchronous synaptic transmission.
    Neuron. 2012 Mar 8;73(5):990-1001 PMID: 22405208
  134. Phospholipid binding by a synaptic vesicle protein homologous to the regulatory region of protein kinase C.
    Nature. 1990 May 17;345(6272):260-3 PMID: 2333096
  135. Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release.
    Science. 2010 Mar 26;327(5973):1614-8 PMID: 20150444
  136. nSec1 binds a closed conformation of syntaxin1A.
    J Cell Biol. 2000 Jan 24;148(2):247-52 PMID: 10648557
  137. Cryo-electron tomography reveals a critical role of RIM1α in synaptic vesicle tethering.
    J Cell Biol. 2013 May 27;201(5):725-40 PMID: 23712261
  138. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy.
    Cell. 1997 Aug 8;90(3):523-35 PMID: 9267032
  139. Three SNARE complexes cooperate to mediate membrane fusion.
    Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8065-70 PMID: 11427709
  140. Complexin cross-links prefusion SNAREs into a zigzag array.
    Nat Struct Mol Biol. 2011 Jul 24;18(8):927-33 PMID: 21785414
  141. Conformational switch of syntaxin-1 controls synaptic vesicle fusion.
    Science. 2008 Sep 12;321(5895):1507-10 PMID: 18703708
  142. Synaptic function is impaired but not eliminated in C. elegans mutants lacking synaptotagmin.
    Cell. 1993 Jul 2;73(7):1291-305 PMID: 8391930
  143. Munc13 C2B domain is an activity-dependent Ca2+ regulator of synaptic exocytosis.
    Nat Struct Mol Biol. 2010 Mar;17(3):280-8 PMID: 20154707
  144. Three-dimensional structure of the neuronal-Sec1-syntaxin 1a complex.
    Nature. 2000 Mar 23;404(6776):355-62 PMID: 10746715
  145. Comparative studies of Munc18c and Munc18-1 reveal conserved and divergent mechanisms of Sec1/Munc18 proteins.
    Proc Natl Acad Sci U S A. 2013 Aug 27;110(35):E3271-80 PMID: 23918365
  146. RIM proteins tether Ca2+ channels to presynaptic active zones via a direct PDZ-domain interaction.
    Cell. 2011 Jan 21;144(2):282-95 PMID: 21241895
Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2013.10.022
Email
[email protected]
Published
2013-10-30
Pages
675-90
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC3866025
Subset
IM
Grants
NIMH NIH HHS · P50 MH086403 · United States
NIDA NIH HHS · R01 DA030379 · United States
NINDS NIH HHS · R01 NS077906 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2013.10.022 PMC Full Text View journal details
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