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Functional Interactions Among the SNARE Regulators UNC-13, Tomosyn, and UNC-18

  • Chapter
Molecular Mechanisms of Neurotransmitter Release

Part of the book series: Contemporary Neuroscience ((NEUROBIOL))

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Abstract

Neurotransmitters are released from secretory vesicles following calcium-triggered fusion with the plasma membrane. These exocytotic events are driven by assembly of tertiary soluble N-ethylmaleimide–sensitive factor attachment receptor (SNARE) complexes among the vesicle SNARE, synaptobrevin, the plasma membrane-associated SNAREs, syntaxin, and synaptosome-associated protein of 25 kDa (SNAP-25). Proteins that effect SNARE complex assembly are thus important regulators of synaptic strength. This chapter reviews our current understanding of the roles played by three SNARE interacting proteins: UNC-13(Munc13), TOM-1(tomosyn) and UNC-18(Munc18). We discuss studies from both invertebrate and vertebrate model systems, highlighting recent advances, the current consensus on molecular mechanisms of action, and unresolved aspects of their function.

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References

  1. Ceccarelli B, Grohovaz F, Hurlbut WP. Freeze-fracture studies of frog neuromuscular junctions during intense release of neurotransmitter. II. Effects of electrical stimulation and high potassium. J Cell Biol 1979;81(1):178–192.

    Article  CAS  PubMed  Google Scholar 

  2. Heuser JE, Reese TS, Dennis MJ, Jan Y, Jan L, Evans L. Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release. J Cell Biol 1979;81(2):275–300.

    Article  CAS  PubMed  Google Scholar 

  3. Sabatini BL, Regehr WG. Timing of neurotransmission at fast synapses in the mammalian brain. Nature 1996;384(6605):170–172.

    Article  CAS  PubMed  Google Scholar 

  4. Sollner T, Whiteheart SW, Brunner M, et al. SNAP receptors implicated in vesicle targeting and fusion. Nature 1993;362(6418):318–324.

    Article  CAS  PubMed  Google Scholar 

  5. Broadie K, Prokop A, Bellen HJ, O’Kane CJ, Schulze KL, Sweeney ST. Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. Neuron 1995;15(3):663–673.

    Article  CAS  PubMed  Google Scholar 

  6. Hanson PI, Roth R, Morisaki H, Jahn R, Heuser JE. Structure and conformational changes in NSF and its membrane receptor complexes visualized by quick-freeze/deep-etch electron microscopy. Cell 1997;90(3):523–535.

    Article  CAS  PubMed  Google Scholar 

  7. Lonart G, Sudhof TC. Assembly of SNARE core complexes prior to neurotransmitter release sets the readily releasable pool of synaptic vesicles. J Biol Chem 2000;275(36): 27703–27707.

    CAS  PubMed  Google Scholar 

  8. Chen YA, Scales SJ, Scheller RH. Sequential SNARE assembly underlies priming and triggering of exocytosis. Neuron 2001;30(1):161–170.

    Article  CAS  PubMed  Google Scholar 

  9. Chen YA, Scheller RH. SNARE-mediated membrane fusion. Nat Rev Mol Cell Biol 2001;2(2):98–106.

    Article  CAS  PubMed  Google Scholar 

  10. Lin RC, Scheller RH. Structural organization of the synaptic exocytosis core complex. Neuron 1997;19(5):1087–1094.

    Article  CAS  PubMed  Google Scholar 

  11. Sutton RB, Fasshauer D, Jahn R, Brunger AT. Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature 1998;395(6700):347–353.

    Article  CAS  PubMed  Google Scholar 

  12. Hammarlund M, Palfreyman MT, Watanabe S, Olsen S, Jorgensen EM. Open syntaxin docks synaptic vesicles. PLoS Biol 2007;5(8):e198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Weimer RM, Gracheva EO, Meyrignac O, Miller KG, Richmond JE, Bessereau JL. UNC-13 and UNC-10/rim localize synaptic vesicles to specific membrane domains. J Neurosci 2006;26(31):8040–8047.

    Article  CAS  PubMed  Google Scholar 

  14. Dulubova I, Sugita S, Hill S, et al. A conformational switch in syntaxin during exocytosis: role of munc18. EMBO J 1999;18(16):4372–4382.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Pevsner J, Hsu SC, Scheller RH. n-Sec1: a neural-specific syntaxin-binding protein. Proc Natl Acad Sci USA 1994;91(4):1445–1449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Sassa T, Harada S, Ogawa H, Rand JB, Maruyama IN, Hosono R. Regulation of the UNC-18– Caenorhabditis elegans syntaxin complex by UNC-13. J Neurosci 1999;19(12):4772–4777.

    CAS  PubMed  Google Scholar 

  17. Betz A, Okamoto M, Benseler F, Brose N. Direct interaction of the rat unc-13 homologue Munc13–1 with the N terminus of syntaxin. J Biol Chem 1997;272(4):2520–2526.

    Article  CAS  PubMed  Google Scholar 

  18. Madison JM, Nurrish S, Kaplan JM. UNC-13 interaction with syntaxin is required for synaptic transmission. Curr Biol 2005;15(24):2236–2242.

    Article  CAS  PubMed  Google Scholar 

  19. Fujita Y, Shirataki H, Sakisaka T, et al. Tomosyn: a syntaxin-1–binding protein that forms a novel complex in the neurotransmitter release process. Neuron 1998;20(5):905–915.

    Article  CAS  PubMed  Google Scholar 

  20. Gracheva EO, Burdina AO, Holgado AM, et al. Tomosyn inhibits synaptic vesicle priming in Caenorhabditis elegans. PLoS Biol 2006;4(8):e261.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Brenner S. The genetics of Caenorhabditis elegans. Genetics 1974;77(1):71–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Saifee O, Wei L, Nonet ML. The Caenorhabditis elegans unc-64 locus encodes a syntaxin that interacts genetically with synaptobrevin. Mol Biol Cell 1998;9(6):1235–1252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Toonen RF, Verhage M. Vesicle trafficking: pleasure and pain from SM genes. Trends Cell Biol 2003;13(4):177–186.

    Article  CAS  PubMed  Google Scholar 

  24. Novick P, Schekman R. Secretion and cell-surface growth are blocked in a temperature-sensitive mutant of Saccharomyces cerevisiae. Proc Natl Acad Sci USA 1979;76(4):1858–1862.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hata Y, Slaughter CA, Sudhof TC. Synaptic vesicle fusion complex contains unc-18 homologue bound to syntaxin. Nature 1993;366(6453):347–351.

    Article  CAS  PubMed  Google Scholar 

  26. Harrison SD, Broadie K, van de Goor J, Rubin GM. Mutations in the Drosophila Rop gene suggest a function in general secretion and synaptic transmission. Neuron 1994;13(3):555–566.

    Article  CAS  PubMed  Google Scholar 

  27. Misura KM, Scheller RH, Weis WI. Three-dimensional structure of the neuronal-Sec1–syntaxin. Nature 2000;404(6776):355–362.

    Article  CAS  PubMed  Google Scholar 

  28. Bracher A, Weissenhorn W. Crystal structures of neuronal squid Sec1 implicate inter-domain hinge movement in the release of t-SNAREs. J Mol Biol 2001;306(1):7–13.

    Article  CAS  PubMed  Google Scholar 

  29. Bracher A, Weissenhorn W. Structural basis for the Golgi membrane recruitment of Sly1p by Sed5p. EMBO J 2002;21(22):6114–6124.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hu SH, Latham CF, Gee CL, James DE, Martin JL. Structure of the Munc18c/Syntaxin4 N-peptide complex defines universal features of the N-peptide binding mode of Sec1/Munc18 proteins. Proc Natl Acad Sci U S A 2007;104(21):8773–8778.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rizo J, Sudhof TC. SNAREs and Munc18 in synaptic vesicle fusion. Nature Rev Neurosci 2002;3(8):641–653.

    Article  CAS  Google Scholar 

  32. Gallwitz D, Jahn R. The riddle of the Sec1/Munc-18 proteins - new twists added to their interactions with SNAREs. Trends Biochem Sci 2003;28(3):113–116.

    Article  CAS  PubMed  Google Scholar 

  33. Schekman R, Novick P. 23 genes, 23 years later. Cell 2004;116(2 suppl):S13–15, 1 p. following S9.

    Article  CAS  PubMed  Google Scholar 

  34. Weimer RM, Richmond JE, Davis WS, Hadwiger G, Nonet ML, Jorgensen EM. Defects in synaptic vesicle docking in unc-18 mutants. Nat Neurosci 2003;6(10):1023–1030.

    Article  CAS  PubMed  Google Scholar 

  35. Verhage M, Maia AS, Plomp JJ, et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 2000;287(5454):864–869.

    Article  CAS  PubMed  Google Scholar 

  36. Voets T, Toonen RF, Brian EC, et al. Munc18–1 promotes large dense-core vesicle docking. Neuron 2001;31(4):581–591.

    Article  CAS  PubMed  Google Scholar 

  37. Toonen RF, Wierda K, Sons MS, et al. Munc18–1 expression levels control synapse recovery by regulating readily releasable pool size. Proc Natl Acad Sci USA 2006;103(48):18332–18337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rostaing P, Real E, Siksou L, et al. Analysis of synaptic ultrastructure without fixative using high-pressure freezing and tomography. Eur J Neurosci 2006;24(12):3463–3474.

    Article  PubMed  Google Scholar 

  39. Wojcik SM, Brose N. Regulation of membrane fusion in synaptic excitation-secretion coupling: speed and accuracy matter. Neuron 2007;55(1):11–24.

    Article  CAS  PubMed  Google Scholar 

  40. Nofal S, Becherer U, Hof D, Matti U, Rettig J. Primed vesicles can be distinguished from docked vesicles by analyzing their mobility. J Neurosci 2007;27(6):1386–1395.

    Article  CAS  PubMed  Google Scholar 

  41. Toonen RF, Kochubey O, de Wit H, et al. Dissecting docking and tethering of secretory vesicles at the target membrane. EMBO J 2006;25(16):3725–3737.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. de Wit H, Cornelisse LN, Toonen RF, Verhage M. Docking of secretory vesicles is syntaxin dependent. PLoS ONE 2006;1:e126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Marsal J, Ruiz-Montasell B, Blasi J, et al. Block of transmitter release by botulinum C1 action on syntaxin at the squid giant synapse. Proc Natl Acad Sci USA 1997;94(26):14871–14876.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. O’Connor V, Heuss C, De Bello WM, et al. Disruption of syntaxin-mediated protein interactions blocks neurotransmitter secretion. Proc Natl Acad Sci USA 1997;94(22):12186–12191.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Richmond JE, Davis WS, Jorgensen EM. UNC-13 is required for synaptic vesicle fusion in C. elegans. Nat Neurosci 1999;2(11):959–964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kidokoro Y. Roles of SNARE proteins and synaptotagmin I in synaptic transmission: studies at the Drosophila neuromuscular synapse. Neurosignals 2003;12(1):13–30.

    Article  CAS  PubMed  Google Scholar 

  47. Yang B, Steegmaier M, Gonzalez LC, Jr., Scheller RH. nSec1 binds a closed conformation of syntaxin1A. J Cell Biol 2000;148(2):247–252.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Schulze KL, Littleton JT, Salzberg A, et al. rop, a Drosophila homolog of yeast Sec1 and vertebrate n-Sec1/Munc-18 proteins, is a negative regulator of neurotransmitter release in vivo. Neuron 1994;13(5):1099–1108.

    Article  CAS  PubMed  Google Scholar 

  49. Dresbach T, Burns ME, O’Connor V, DeBello WM, Betz H, Augustine GJ. A neuronal Sec1 homolog regulates neurotransmitter release at the squid giant synapse. J Neurosci 1998;18(8):2923–2932.

    CAS  PubMed  Google Scholar 

  50. Rickman C, Medine CN, Bergmann A, Duncan RR. Functionally and spatially distinct modes of munc18–syntaxin 1 interaction. J Biol Chem 2007;282(16):12097–12103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Gulyas-Kovacs A, de Wit H, Milosevic I, et al. Munc18–1: sequential interactions with the fusion machinery stimulate vesicle docking and priming. J Neurosci 2007;27(32):8676–8686.

    Article  CAS  PubMed  Google Scholar 

  52. Dulubova I, Yamaguchi T, Gao Y, et al. How Tlg2p/syntaxin 16 ‘snares’ Vps45. EMBO J 2002;21(14):3620–3631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yamaguchi T, Dulubova I, Min SW, Chen X, Rizo J, Sudhof TC. Sly1 binds to Golgi and ER syntaxins via a conserved N-terminal peptide motif. Dev Cell 2002;2(3):295–305.

    Article  CAS  PubMed  Google Scholar 

  54. Zilly FE, Sorensen JB, Jahn R, Lang T. Munc18–bound syntaxin readily forms SNARE complexes with synaptobrevin in native plasma membranes. PLoS Biol 2006;4(10):e330.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Shen J, Tareste DC, Paumet F, Rothman JE, Melia TJ. Selective activation of cognate SNAREpins by Sec1/Munc18 proteins. Cell 2007;128(1):183–195.

    Article  CAS  PubMed  Google Scholar 

  56. Dulubova I, Khvotchev M, Liu S, Huryeva I, Sudhof TC, Rizo J. Munc18–1 binds directly to the neuronal SNARE complex. Proc Natl Acad Sci USA 2007;104(8):2697–2702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Carr CM, Grote E, Munson M, Hughson FM, Novick PJ. Sec1p binds to SNARE complexes and concentrates at sites of secretion. J Cell Biol 1999;146(2):333–344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Peng R, Gallwitz D. Multiple SNARE interactions of an SM protein: Sed5p/Sly1p binding is dispensable for transport. Embo J 2004;23(20):3939–3949.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Scott BL, Van Komen JS, Irshad H, Liu S, Wilson KA, McNew JA. Sec1p directly stimulates SNARE-mediated membrane fusion in vitro. J Cell Biol 2004;167(1):75–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Carpp LN, Ciufo LF, Shanks SG, Boyd A, Bryant NJ. The Sec1p/Munc18 protein Vps45p binds its cognate SNARE proteins via two distinct modes. J Cell Biol 2006;173(6):927–936.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Togneri J, Cheng YS, Munson M, Hughson FM, Carr CM. Specific SNARE complex binding mode of the Sec1/Munc-18 protein, Sec1p. Proc Natl Acad Sci USA 2006;103(47):17730–17735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Xu XZ, Wes PD, Chen H, et al. Retinal targets for calmodulin include proteins implicated in synaptic transmission. J Biol Chem 1998;273(47):31297–31307.

    Article  CAS  PubMed  Google Scholar 

  63. Brose N, Hofmann K, Hata Y, Sudhof TC. Mammalian homologues of Caenorhabditis elegans unc-13 gene define novel family of C2–domain proteins. J Biol Chem 1995;270(42):25273–25280.

    Article  CAS  PubMed  Google Scholar 

  64. Koch H, Hofmann K, Brose N. Definition of Munc13–homology-domains and characterization of a novel ubiquitously expressed Munc13 isoform. Biochem J 2000;349(pt 1):247–253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kohn RE, Duerr JS, McManus JR, et al. Expression of multiple UNC-13 proteins in the C. elegans nervous system. Mol Biol Cell 2000;11(10):3441–3452.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Aravamudan B, Fergestad T, Davis WS, Rodesch CK, Broadie K. Drosophila UNC-13 is essential for synaptic transmission. Nat Neurosci 1999;2(11):965–971.

    Article  CAS  PubMed  Google Scholar 

  67. Augustin I, Betz A, Herrmann C, Jo T, Brose N. Differential expression of two novel Munc13 proteins in rat brain. Biochem J 1999;337(pt 3):363–371.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Augustin I, Korte S, Rickmann M, et al. The cerebellum-specific Munc13 isoform Munc13–3 regulates cerebellar synaptic transmission and motor learning in mice. J Neurosci 2001;21(1):10–17.

    CAS  PubMed  Google Scholar 

  69. Yang CB, Zheng YT, Li GY, Mower GD. Identification of Munc13–3 as a candidate gene for critical-period neuroplasticity in visual cortex. J Neurosci 2002;22(19):8614–8618.

    CAS  PubMed  Google Scholar 

  70. Varoqueaux F, Sigler A, Rhee JS, et al. Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13–mediated vesicle priming. Proc Natl Acad Sci USA 2002;99(13):9037–9042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Augustin I, Rosenmund C, Sudhof TC, Brose N. Munc13–1 is essential for fusion competence of glutamatergic synaptic vesicles. Nature 1999;400(6743):457–461.

    Article  CAS  PubMed  Google Scholar 

  72. Ashery U, Varoqueaux F, Voets T, et al. Munc13–1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells. EMBO J 2000;19(14):3586–3596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zhen M, Jin Y. Presynaptic terminal differentiation: transport and assembly. Curr Opin Neurobiol 2004;14(3):280–287.

    Article  CAS  PubMed  Google Scholar 

  74. Basu J, Shen N, Dulubova I, et al. A minimal domain responsible for Munc13 activity. Nat Struct Mol Biol 2005;12(11):1017–1018.

    Article  CAS  PubMed  Google Scholar 

  75. Stevens DR, Wu ZX, Matti U, et al. Identification of the minimal protein domain required for priming activity of Munc13–1. Curr Biol 2005;15(24):2243–2248.

    Article  CAS  PubMed  Google Scholar 

  76. Brose N, Rosenmund C, Rettig J. Regulation of transmitter release by Unc-13 and its homologues. Curr Opin Neurobiol 2000;10(3):303–311.

    Article  CAS  PubMed  Google Scholar 

  77. Richmond JE, Weimer RM, Jorgensen EM. An open form of syntaxin bypasses the requirement for UNC-13 in vesicle priming. Nature 2001;412(6844):338–341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. McEwen JM, Madison JM, Dybbs M, Kaplan JM. Antagonistic regulation of synaptic vesicle priming by Tomosyn and UNC-13. Neuron 2006;51(3):303–315.

    Article  CAS  PubMed  Google Scholar 

  79. Basu J, Betz A, Brose N, Rosenmund C. Munc13–1 C1 domain activation lowers the energy barrier for synaptic vesicle fusion. J Neurosci 2007;27(5):1200–1210.

    Article  CAS  PubMed  Google Scholar 

  80. Groffen AJ, Friedrich R, Brian EC, Ashery U, Verhage M. DOC2A and DOC2B are sensors for neuronal activity with unique calcium-dependent and kinetic properties. J Neurochem 2006;97(3):818–833.

    Article  CAS  PubMed  Google Scholar 

  81. Kagami M, Toh-e A, Matsui Y. Sro7p, a Saccharomyces cerevisiae counterpart of the tumor suppressor l(2)gl protein, is related to myosins in function. Genetics 1998;149(4):1717–1727.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Lehman K, Rossi G, Adamo JE, Brennwald P. Yeast homologues of tomosyn and lethal giant larvae function in exocytosis and are associated with the plasma membrane SNARE, Sec9. J Cell Biol 1999;146(1):125–140.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mechler BM, McGinnis W, Gehring WJ. Molecular cloning of lethal(2)giant larvae, a recessive oncogene of Drosophila melanogaster. EMBO J 1985;4(6):1551–1557.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Musch A, Cohen D, Yeaman C, Nelson WJ, Rodriguez-Boulan E, Brennwald PJ. Mammalian homolog of Drosophila tumor suppressor lethal (2) giant larvae interacts with basolateral exocytic machinery in Madin-Darby canine kidney cells. Mol Biol Cell 2002;13(1):158–168.

    Article  CAS  PubMed  Google Scholar 

  85. Scales SJ, Hesser BA, Masuda ES, Scheller RH. Amisyn, a novel syntaxin-binding protein that may regulate SNARE complex assembly. J Biol Chem 2002;277(31):28271–28279.

    Article  CAS  PubMed  Google Scholar 

  86. Masuda ES, Huang BC, Fisher JM, Luo Y, Scheller RH. Tomosyn binds t-SNARE proteins via a VAMP-like coiled coil. Neuron 1998;21(3):479–480.

    Article  CAS  PubMed  Google Scholar 

  87. Hattendorf DA, Andreeva A, Gangar A, Brennwald PJ, Weis WI. Structure of the yeast polarity protein Sro7 reveals a SNARE regulatory mechanism. Nature 2007;446(7135):567–571.

    Article  CAS  PubMed  Google Scholar 

  88. Dybbs M, Ngai J, Kaplan JM. Using microarrays to facilitate positional cloning: identification of tomosyn as an inhibitor of neurosecretion. PLoS Genet 2005;1(1):6–16.

    Article  CAS  PubMed  Google Scholar 

  89. Zhang W, Lilja L, Mandic SA, et al. Tomosyn is expressed in beta-cells and negatively regulates insulin exocytosis. Diabetes 2006;55(3):574–581.

    Article  CAS  PubMed  Google Scholar 

  90. Hatsuzawa K, Lang T, Fasshauer D, Bruns D, Jahn R. The R-SNARE motif of tomosyn forms SNARE core complexes with syntaxin 1 and SNAP-25 and down-regulates exocytosis. J Biol Chem 2003;278(33):31159–31166.

    Article  CAS  PubMed  Google Scholar 

  91. Widberg CH, Bryant NJ, Girotti M, Rea S, James DE. Tomosyn interacts with the t-SNAREs syntaxin4 and SNAP23 and plays a role in insulin-stimulated GLUT4 translocation. J Biol Chem 2003;278(37):35093–35101.

    Article  CAS  PubMed  Google Scholar 

  92. Yizhar O, Matti U, Melamed R, et al. Tomosyn inhibits priming of large dense-core vesicles in a calcium-dependent manner. Proc Natl Acad Sci U S A 2004;101(8):2578–2583.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Baba T, Sakisaka T, Mochida S, Takai Y. PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter. J Cell Biol 2005;170(7):1113–1125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Cheviet S, Bezzi P, Ivarsson R, et al. Tomosyn-1 is involved in a post-docking event required for pancreatic beta-cell exocytosis. J Cell Sci 2006;119(pt 14):2912–2920.

    Article  CAS  PubMed  Google Scholar 

  95. Sakisaka T, Baba T, Tanaka S, Izumi G, Yasumi M, Takai Y. Regulation of SNAREs by tomosyn and ROCK: implication in extension and retraction of neurites. J Cell Biol 2004;166(1):17–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Manfruelli P, Arquier N, Hanratty WP, Semeriva M. The tumor suppressor gene, lethal(2)giant larvae (1(2)g1), is required for cell shape change of epithelial cells during Drosophila development. Development 1996;122(7):2283–2294.

    CAS  PubMed  Google Scholar 

  97. Pobbati AV, Razeto A, Boddener M, Becker S, Fasshauer D. Structural basis for the inhibitory role of tomosyn in exocytosis. J Biol Chem 2004;279(45):47192–47200.

    Article  CAS  PubMed  Google Scholar 

  98. Reim K, Mansour M, Varoqueaux F, et al. Complexins regulate a late step in Ca2+-dependent neurotransmitter release. Cell 2001;104(1):71–81.

    Article  CAS  PubMed  Google Scholar 

  99. Constable JR, Graham ME, Morgan A, Burgoyne RD. Amisyn regulates exocytosis and fusion pore stability by both syntaxin-dependent and syntaxin-independent mechanisms. J Biol Chem 2005;280(36):31615–31623.

    Article  CAS  PubMed  Google Scholar 

  100. Yizhar O, Lipstein N, Gladycheva SE, et al. Multiple functional domains are involved in tomosyn regulation of exocytosis. J Neurochem 2007;103(2):604–616.

    Article  CAS  PubMed  Google Scholar 

  101. Wierda KD, Toonen RF, de Wit H, Brussaard AB, Verhage M. Interdependence of PKC-dependent and PKC-independent pathways for presynaptic plasticity. Neuron 2007;54(2): 275–290.

    Article  CAS  PubMed  Google Scholar 

  102. Palfreyman M, Jorgensen EM. PKC defends crown against Munc13. Neuron 2007;54(2):179–180.

    Article  CAS  PubMed  Google Scholar 

  103. Dulubova I, Lou X, Lu J, et al. A Munc13/RIM/Rab3 tripartite complex: from priming to plasticity? EMBO J 2005;24(16):2839–2850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Gladycheva SE, Ho CS, Lee YY, Stuenkel EL. Regulation of Syntaxin1A/Munc18 complex for SNARE Pairing. J Physiol 2004;558(Pt3):857–871.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Gladycheva SE, Lam AD, Liu J, et al. Receptor-mediated regulation of tomosyn-syntaxin 1A interactions in bovine adrenal chromaffin cells. J Biol Chem 2007;282(31):22887–22899.

    Article  CAS  PubMed  Google Scholar 

  106. Gracheva EO, Burdina AO, Touroutine D, Berthelot-Grosjean M, Parekh H, Richmond JE. Tomosyn negatively regulates both synaptic transmitter and neuropeptide release at the C. elegans neuromuscular junction. J Physiol 2007;585(Pt3):705–709.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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  1. Genentech, South San Francisco, CA, USA

    Robby M. Weimer

  2. Biological Sciences Department, University of Illinois at Chicago, Chicago, IL, 60607, USA

    Janet E. Richmond

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  1. Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, USA

    Zhao-Wen Wang Ph.D.

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Weimer, R.M., Richmond, J.E. (2008). Functional Interactions Among the SNARE Regulators UNC-13, Tomosyn, and UNC-18. In: Wang, ZW. (eds) Molecular Mechanisms of Neurotransmitter Release. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-481-0_7

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