Gene Symbol: Syt1
Description: synaptotagmin I
Alias: AW124717, G630098F17Rik, SytI, synaptotagmin-1, p65
Species: mouse
Products:     Syt1

Top Publications

  1. Xue M, Ma C, Craig T, Rosenmund C, Rizo J. The Janus-faced nature of the C(2)B domain is fundamental for synaptotagmin-1 function. Nat Struct Mol Biol. 2008;15:1160-8 pubmed publisher
  2. Mayanil C, Knepper P. Synaptic vesicle and synaptic membrane glycoproteins during pre- and postnatal development of mouse cerebral cortex, cerebellum and spinal cord. Dev Neurosci. 1993;15:133-45 pubmed
    ..The developmental expression of synaptotagmin 1, a well characterized glycoprotein of synaptic vesicle, was determined by immunoblots analysis...
  3. Li L, Shin O, Rhee J, Arac D, Rah J, Rizo J, et al. Phosphatidylinositol phosphates as co-activators of Ca2+ binding to C2 domains of synaptotagmin 1. J Biol Chem. 2006;281:15845-52 pubmed
    Ca2+-dependent phospholipid binding to the C2A and C2B domains of synaptotagmin 1 is thought to trigger fast neurotransmitter release, but only Ca2+ binding to the C2B domain is essential for release...
  4. Sørensen J, Fernandez Chacon R, Sudhof T, Neher E. Examining synaptotagmin 1 function in dense core vesicle exocytosis under direct control of Ca2+. J Gen Physiol. 2003;122:265-76 pubmed
    We tested the long-standing hypothesis that synaptotagmin 1 is the Ca2+ sensor for fast neurosecretion by analyzing the intracellular Ca2+ dependence of large dense-core vesicle exocytosis in a mouse strain carrying a mutated ..
  5. Walther K, Diril M, Jung N, Haucke V. Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin. Proc Natl Acad Sci U S A. 2004;101:964-9 pubmed
    ..We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling. ..
  6. Xu J, Mashimo T, Sudhof T. Synaptotagmin-1, -2, and -9: Ca(2+) sensors for fast release that specify distinct presynaptic properties in subsets of neurons. Neuron. 2007;54:567-81 pubmed
  7. Gerber S, Rah J, Min S, Liu X, de Wit H, Dulubova I, et al. Conformational switch of syntaxin-1 controls synaptic vesicle fusion. Science. 2008;321:1507-10 pubmed publisher
    ..Thus, the closed conformation of syntaxin-1 gates the initiation of the synaptic vesicle fusion reaction, which is then mediated by SNARE-complex/Munc18-1 assemblies. ..
  8. Rummel A, Karnath T, Henke T, Bigalke H, Binz T. Synaptotagmins I and II act as nerve cell receptors for botulinum neurotoxin G. J Biol Chem. 2004;279:30865-70 pubmed
    ..In addition, we show that the carboxyl-terminal domain of the cell binding fragment of BoNT/B and BoNT/G mediates the interaction with their protein receptor. ..
  9. Dong M, Richards D, Goodnough M, Tepp W, Johnson E, Chapman E. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J Cell Biol. 2003;162:1293-303 pubmed
    ..Finally, we show that syt II fragments, in conjunction with gangliosides, neutralized BoNT/B in intact mice. These findings establish that syts I and II can function as protein receptors for BoNT/B. ..

More Information


  1. Shin O, Rhee J, Tang J, Sugita S, Rosenmund C, Sudhof T. Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. Neuron. 2003;37:99-108 pubmed
    Sr(2+) triggers neurotransmitter release similar to Ca(2+), but less efficiently. We now show that in synaptotagmin 1 knockout mice, the fast component of both Ca(2+)- and Sr(2+)-induced release is selectively impaired, suggesting that ..
  2. Geppert M, Goda Y, Hammer R, Li C, Rosahl T, Stevens C, et al. Synaptotagmin I: a major Ca2+ sensor for transmitter release at a central synapse. Cell. 1994;79:717-27 pubmed
    ..We propose that synaptotagmin I is the major low affinity Ca2+ sensor mediating Ca2+ regulation of synchronous neurotransmitter release in hippocampal neurons. ..
  3. Washbourne P, Thompson P, Carta M, Costa E, Mathews J, Lopez Bendito G, et al. Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nat Neurosci. 2002;5:19-26 pubmed
    ..These results demonstrate that the development of neurotransmission requires the recruitment of a specialized SNARE core complex to meet the demands of regulated exocytosis. ..
  4. Voets T, Moser T, Lund P, Chow R, Geppert M, Sudhof T, et al. Intracellular calcium dependence of large dense-core vesicle exocytosis in the absence of synaptotagmin I. Proc Natl Acad Sci U S A. 2001;98:11680-5 pubmed
    ..Alternatively, synaptotagmin I could function as calcium sensor for the readily releasable pool, leading to the destabilization of the pool in its absence. ..
  5. Cao P, Yang X, Sudhof T. Complexin activates exocytosis of distinct secretory vesicles controlled by different synaptotagmins. J Neurosci. 2013;33:1714-27 pubmed publisher
  6. Yao J, Kwon S, Gaffaney J, Dunning F, Chapman E. Uncoupling the roles of synaptotagmin I during endo- and exocytosis of synaptic vesicles. Nat Neurosci. 2011;15:243-9 pubmed publisher
    Synaptotagmin I (syt1) is required for normal rates of synaptic vesicle endo- and exocytosis...
  7. Yang X, Kaeser Woo Y, Pang Z, Xu W, Sudhof T. Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory ? helix. Neuron. 2010;68:907-20 pubmed publisher
    ..Thus, complexin performs mechanistically distinct activation and clamping functions that operate in conjunction with synaptotagmin-1 by controlling trans-SNARE-complex assembly. ..
  8. Nishiki T, Augustine G. Synaptotagmin I synchronizes transmitter release in mouse hippocampal neurons. J Neurosci. 2004;24:6127-32 pubmed
    ..Thus, synaptotagmin I synchronizes the rapid release of neurotransmitters after Ca2+ entry into presynaptic terminals and also appears to suppress the slower, asynchronous form of transmitter release. ..
  9. Nagy G, Kim J, Pang Z, Matti U, Rettig J, Sudhof T, et al. Different effects on fast exocytosis induced by synaptotagmin 1 and 2 isoforms and abundance but not by phosphorylation. J Neurosci. 2006;26:632-43 pubmed
    Synaptotagmins comprise a large protein family, of which synaptotagmin 1 (Syt1) is a Ca2+ sensor for fast exocytosis, and its close relative, synaptotagmin 2 (Syt2), is assumed to serve similar functions...
  10. Maximov A, Sudhof T. Autonomous function of synaptotagmin 1 in triggering synchronous release independent of asynchronous release. Neuron. 2005;48:547-54 pubmed
    ..Ca(2+) triggers neurotransmitter release in at least two principal modes, synchronous and asynchronous release. Synaptotagmin 1 functions as a Ca(2+) sensor for synchronous release, but its role in asynchronous release remains unclear...
  11. Li C, Ullrich B, Zhang J, Anderson R, Brose N, Sudhof T. Ca(2+)-dependent and -independent activities of neural and non-neural synaptotagmins. Nature. 1995;375:594-9 pubmed
    ..The same C2 domains also bind syntaxin as a function of Ca2+ but the Ca(2+)-concentration dependence of Syt I, II and V (> 200 microM) differs from that of Syt III and VII (< 10 microM).(ABSTRACT TRUNCATED AT 250 WORDS) ..
  12. Borisovska M, Zhao Y, Tsytsyura Y, Glyvuk N, Takamori S, Matti U, et al. v-SNAREs control exocytosis of vesicles from priming to fusion. EMBO J. 2005;24:2114-26 pubmed
    ..We demonstrate that dynamics of fusion pore dilation are regulated by v-SNAREs, indicating their action throughout exocytosis from priming to fusion of vesicles. ..
  13. Xu J, Pang Z, Shin O, Sudhof T. Synaptotagmin-1 functions as a Ca2+ sensor for spontaneous release. Nat Neurosci. 2009;12:759-66 pubmed publisher
    ..that >95% of spontaneous release in murine cortical neurons was induced by Ca2+-binding to synaptotagmin-1 (Syt1), the Ca2+ sensor for fast synchronous neurotransmitter release...
  14. Yao J, Gaffaney J, Kwon S, Chapman E. Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release. Cell. 2011;147:666-77 pubmed publisher
    ..In summary, we propose that Doc2 is a Ca(2+) sensor that is kinetically tuned to regulate asynchronous neurotransmitter release. ..
  15. Fernandez Chacon R, Shin O, Königstorfer A, Matos M, Meyer A, Garcia J, et al. Structure/function analysis of Ca2+ binding to the C2A domain of synaptotagmin 1. J Neurosci. 2002;22:8438-46 pubmed
    b>Synaptotagmin 1, a Ca2+ sensor for fast synaptic vesicle exocytosis, contains two C2 domains that form Ca2+-dependent complexes with phospholipids...
  16. Kerr A, Reisinger E, Jonas P. Differential dependence of phasic transmitter release on synaptotagmin 1 at GABAergic and glutamatergic hippocampal synapses. Proc Natl Acad Sci U S A. 2008;105:15581-6 pubmed publisher
    Previous studies revealed that synaptotagmin 1 is the major Ca(2+) sensor for fast synchronous transmitter release at excitatory synapses...
  17. Kwon S, Chapman E. Glycosylation is dispensable for sorting of synaptotagmin 1 but is critical for targeting of SV2 and synaptophysin to recycling synaptic vesicles. J Biol Chem. 2012;287:35658-68 pubmed publisher
    ..For example, the three major synaptic vesicle glycoproteins, synaptotagmin 1, synaptophysin, and SV2, represent ?30% of the total copy number of vesicle proteins...
  18. de Wit H, Walter A, Milosevic I, Gulyas Kovacs A, Riedel D, Sørensen J, et al. Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes. Cell. 2009;138:935-46 pubmed publisher
  19. Fox M, Sanes J. Synaptotagmin I and II are present in distinct subsets of central synapses. J Comp Neurol. 2007;503:280-96 pubmed
    b>Synaptotagmin 1 and 2 (syt 1, syt 2) are synaptic vesicle-associated membrane proteins that act as calcium sensors for fast neurotransmitter release from presynaptic nerve terminals...
  20. Burgalossi A, Jung S, Meyer G, Jockusch W, Jahn O, Taschenberger H, et al. SNARE protein recycling by ?SNAP and ?SNAP supports synaptic vesicle priming. Neuron. 2010;68:473-87 pubmed publisher
    ..Our analysis of ?- and ?SNAP deletion mutant neurons shows that the two NSF cofactors support synaptic vesicle priming by determining the availability of free SNARE components, particularly during phases of high synaptic activity. ..
  21. Tang J, Maximov A, Shin O, Dai H, Rizo J, Sudhof T. A complexin/synaptotagmin 1 switch controls fast synaptic vesicle exocytosis. Cell. 2006;126:1175-87 pubmed
    Ca(2+) binding to synaptotagmin 1 triggers fast exocytosis of synaptic vesicles that have been primed for release by SNARE-complex assembly. Besides synaptotagmin 1, fast Ca(2+)-triggered exocytosis requires complexins...
  22. Rhee J, Li L, Shin O, Rah J, Rizo J, Sudhof T, et al. Augmenting neurotransmitter release by enhancing the apparent Ca2+ affinity of synaptotagmin 1. Proc Natl Acad Sci U S A. 2005;102:18664-9 pubmed
    b>Synaptotagmin 1 likely acts as a Ca2+ sensor in neurotransmitter release by Ca2+-binding to its two C2 domains...
  23. Nicholson Tomishima K, Ryan T. Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I. Proc Natl Acad Sci U S A. 2004;101:16648-52 pubmed
    ..basis of this coupling is poorly understood, numerous biochemical data point to a role for synaptotagmin I (SytI), an essential synaptic vesicle protein required for fast calcium-dependent exocytosis...
  24. Fernandez Chacon R, Königstorfer A, Gerber S, Garcia J, Matos M, Stevens C, et al. Synaptotagmin I functions as a calcium regulator of release probability. Nature. 2001;410:41-9 pubmed
    ..Therefore, Ca2+ binding to synaptotagmin I participates in triggering neurotransmitter release at the synapse. ..
  25. Schonn J, Maximov A, Lao Y, Sudhof T, Sørensen J. Synaptotagmin-1 and -7 are functionally overlapping Ca2+ sensors for exocytosis in adrenal chromaffin cells. Proc Natl Acad Sci U S A. 2008;105:3998-4003 pubmed publisher
  26. Kohli B, Pflieger D, Mueller L, Carbonetti G, Aebersold R, Nitsch R, et al. Interactome of the amyloid precursor protein APP in brain reveals a protein network involved in synaptic vesicle turnover and a close association with Synaptotagmin-1. J Proteome Res. 2012;11:4075-90 pubmed publisher
  27. Pang Z, Shin O, Meyer A, Rosenmund C, Sudhof T. 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;26:12556-65 pubmed
    ..These data establish that fast vesicle exocytosis is driven by a dual Ca2+-dependent activity of synaptotagmin-1, namely Ca2+-dependent binding both to SNARE complexes and to phospholipids. ..
  28. Bhalla A, Tucker W, Chapman E. Synaptotagmin isoforms couple distinct ranges of Ca2+, Ba2+, and Sr2+ concentration to SNARE-mediated membrane fusion. Mol Biol Cell. 2005;16:4755-64 pubmed
    ..Our data demonstrate that different syt isoforms are specialized to sense different ranges of divalent cations and that PS is an essential effector of Ca2+.syt action. ..
  29. Chicka M, Hui E, Liu H, Chapman E. Synaptotagmin arrests the SNARE complex before triggering fast, efficient membrane fusion in response to Ca2+. Nat Struct Mol Biol. 2008;15:827-35 pubmed publisher
    ..These findings demonstrate that Ca(2+) converts synaptotagmin from a clamp to a trigger for exocytosis. ..
  30. Nishiki T, Augustine G. Dual roles of the C2B domain of synaptotagmin I in synchronizing Ca2+-dependent neurotransmitter release. J Neurosci. 2004;24:8542-50 pubmed
  31. Tejero R, Lopez Manzaneda M, Arumugam S, Tabares L. Synaptotagmin-2, and -1, linked to neurotransmission impairment and vulnerability in Spinal Muscular Atrophy. Hum Mol Genet. 2016;25:4703-4716 pubmed publisher
    ..We discovered that synaptotagmin-1 (Syt1) was developmentally downregulated in nerve terminals of highly affected muscles but not in low vulnerable muscles...
  32. Kuzuya A, Zoltowska K, Post K, Arimon M, Li X, Svirsky S, et al. Identification of the novel activity-driven interaction between synaptotagmin 1 and presenilin 1 links calcium, synapse, and amyloid beta. BMC Biol. 2016;14:25 pubmed publisher
    ..Mass spectrometry screen of mouse brain lysates identified synaptotagmin 1 (Syt1) as a novel synapse-specific PS1-binding partner that shows Ca(2+)-dependent PS1 binding profiles in ..
  33. Zhu X, Qi S, Liu J, Chen L, Zhang C, Yang S, et al. Synaptotagmin1 is required for spindle stability and metaphase-to-anaphase transition in mouse oocytes. Cell Cycle. 2012;11:818-26 pubmed publisher
    ..Here, we identified the unique localization, expression and function of Syt1 during mouse oocyte meiotic maturation by using confocal microscopy, western blotting, Morpholino-based knockdown ..
  34. Yowler B, Kensinger R, Schengrund C. Botulinum neurotoxin A activity is dependent upon the presence of specific gangliosides in neuroblastoma cells expressing synaptotagmin I. J Biol Chem. 2002;277:32815-9 pubmed
  35. Bagala C, Kolev V, Mandinova A, Soldi R, Mouta C, Graziani I, et al. The alternative translation of synaptotagmin 1 mediates the non-classical release of FGF1. Biochem Biophys Res Commun. 2003;310:1041-7 pubmed
    ..FGF1, it was not possible to identify a specific intracellular protease responsible for the processing of p65 Syt1. Surprisingly, analysis of the p65 Syt1 coding sequence revealed the presence of two potential alternative ATG ..
  36. Borden C, Stevens C, Sullivan J, Zhu Y. Synaptotagmin mutants Y311N and K326/327A alter the calcium dependence of neurotransmission. Mol Cell Neurosci. 2005;29:462-70 pubmed
    ..We conclude that self-oligomerization is unlikely to play any significant role in triggering synaptic vesicle exocytosis. ..
  37. Xue M, Craig T, Shin O, Li L, Brautigam C, Tomchick D, et al. Structural and mutational analysis of functional differentiation between synaptotagmins-1 and -7. PLoS ONE. 2010;5: pubmed publisher
    ..chimera that contains the synaptotagmin-1 sequence with its C2B domain replaced by the synaptotagmin-7 C2B domain (Syt1/7)...
  38. Powell C, Schoch S, Monteggia L, Barrot M, Matos M, Feldmann N, et al. The presynaptic active zone protein RIM1alpha is critical for normal learning and memory. Neuron. 2004;42:143-53 pubmed
    ..Mice with a synaptotagmin 1 mutation, which selectively lowers release probability, and mice with Rab3A deletion, which selectively ..
  39. Yu Z, Liu N, Wang Y, Li X, Wang X. Identification of neuroglobin-interacting proteins using yeast two-hybrid screening. Neuroscience. 2012;200:99-105 pubmed publisher
    ..Our findings provide molecular targets for investigating protein interaction-based biological functions and neuroprotective mechanisms of Ngb. ..
  40. Kedar G, Munch A, van Weering J, Malsam J, Scheutzow A, de Wit H, et al. A Post-Docking Role of Synaptotagmin 1-C2B Domain Bottom Residues R398/399 in Mouse Chromaffin Cells. J Neurosci. 2015;35:14172-82 pubmed publisher
    Synaptotagmin-1 (Syt1) is the principal Ca(2+) sensor for vesicle fusion and is also essential for vesicle docking in chromaffin cells...
  41. Coate T, Spita N, Zhang K, Isgrig K, Kelley M. Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons. elife. 2015;4: pubmed publisher
    ..These results suggest a model in which cochlear innervation patterns by type I SGNs are determined, at least in part, through a Semaphorin-3F-mediated inhibitory signal that impedes processes from extending beyond the IHC region. ..
  42. Zhou Q, Lai Y, Bacaj T, Zhao M, Lyubimov A, Uervirojnangkoorn M, et al. Architecture of the synaptotagmin-SNARE machinery for neuronal exocytosis. Nature. 2015;525:62-7 pubmed publisher
  43. Hilbush B, Morgan J. A third synaptotagmin gene, Syt3, in the mouse. Proc Natl Acad Sci U S A. 1994;91:8195-9 pubmed
    ..In the most highly conserved C2 domain, the mammalian synaptotagmins, SYT1 and SYT2, share 88% sequence identity, whereas SYT3 has only approximately 45% identity to either...
  44. Gundersen C, Umbach J. Synaptotagmins 1 and 2 as mediators of rapid exocytosis at nerve terminals: the dyad hypothesis. J Theor Biol. 2013;332:149-60 pubmed publisher
    ..The relative simplicity of this model and its amenability to empirical testing provide a useful template for future investigations of the molecular events underlying the exocytotic cascade. ..
  45. Morgado A, Xavier J, Dionísio P, Ribeiro M, Dias R, Sebastião A, et al. MicroRNA-34a Modulates Neural Stem Cell Differentiation by Regulating Expression of Synaptic and Autophagic Proteins. Mol Neurobiol. 2015;51:1168-83 pubmed publisher
    ..In addition, synaptotagmin 1 (Syt1) and autophagy-related 9a (Atg9a) significantly increased during neurogenesis...
  46. Fukuda M. Distinct developmental expression of synaptotagmin I and IX in the mouse brain. Neuroreport. 2006;17:179-82 pubmed
    ..These findings suggest that synaptotagmin IX regulates the transport of certain vesicles in the brain other than synaptic vesicles. ..
  47. Zhang N, Gordon S, Fritsch M, Esoof N, Campbell D, Gourlay R, et al. Phosphorylation of synaptic vesicle protein 2A at Thr84 by casein kinase 1 family kinases controls the specific retrieval of synaptotagmin-1. J Neurosci. 2015;35:2492-507 pubmed publisher
  48. Bacaj T, Wu D, Yang X, Morishita W, Zhou P, Xu W, et al. Synaptotagmin-1 and synaptotagmin-7 trigger synchronous and asynchronous phases of neurotransmitter release. Neuron. 2013;80:947-59 pubmed publisher
  49. Liu Y, Chen H, Yu L, Kuo Y, Wu F, Chuang J, et al. Upregulation of hippocampal TrkB and synaptotagmin is involved in treadmill exercise-enhanced aversive memory in mice. Neurobiol Learn Mem. 2008;90:81-9 pubmed publisher
    ..Taken together, these data suggest that the upregulation of TrkB and synaptotagmin in the hippocampus contributes to the exercise-facilitated aversive memory. ..
  50. Gitler D, Xu Y, Kao H, Lin D, Lim S, Feng J, et al. Molecular determinants of synapsin targeting to presynaptic terminals. J Neurosci. 2004;24:3711-20 pubmed
    ..Domain D inhibited targeting, but this inhibition was overcome by domain E. Thus, multiple intermolecular and intramolecular interactions are required for synapsins to target to presynaptic terminals. ..
  51. Sudhof T, Rizo J. Synaptotagmins: C2-domain proteins that regulate membrane traffic. Neuron. 1996;17:379-88 pubmed
  52. Reisinger E, Bresee C, Neef J, Nair R, Reuter K, Bulankina A, et al. Probing the functional equivalence of otoferlin and synaptotagmin 1 in exocytosis. J Neurosci. 2011;31:4886-95 pubmed publisher
    ..serve as a Ca(2+) sensor in vesicle fusion in IHCs that seem to lack the classical neuronal Ca(2+) sensors synaptotagmin 1 (Syt1) and Syt2...
  53. Watanabe H, Yamashita T, Saitoh N, Kiyonaka S, Iwamatsu A, Campbell K, et al. Involvement of Ca2+ channel synprint site in synaptic vesicle endocytosis. J Neurosci. 2010;30:655-60 pubmed publisher
    ..bind the mu subunit of AP-2, an adaptor protein for clathrin-mediated endocytosis, in competition with the synaptotagmin 1 (Syt 1) C2B domain...