Summary: A family of vesicular transport proteins characterized by an N-terminal transmembrane region and two C-terminal calcium-binding domains.

Top Publications

  1. Pilot F, Philippe J, Lemmers C, Lecuit T. Spatial control of actin organization at adherens junctions by a synaptotagmin-like protein Btsz. Nature. 2006;442:580-4 pubmed
    ..These results provide a mechanism for the spatial order of actin organization underlying junction stabilization in primary embryonic epithelia. ..
  2. Dean C, Dunning F, Liu H, Bomba Warczak E, Martens H, Bharat V, et al. Axonal and dendritic synaptotagmin isoforms revealed by a pHluorin-syt functional screen. Mol Biol Cell. 2012;23:1715-27 pubmed publisher
    The synaptotagmins (syts) are a family of molecules that regulate membrane fusion. There are 17 mammalian syt isoforms, most of which are expressed in the brain...
  3. Potokar M, Stenovec M, Kreft M, Kreft M, Zorec R. Stimulation inhibits the mobility of recycling peptidergic vesicles in astrocytes. Glia. 2008;56:135-44 pubmed
    ..Physiological implications of attenuated traffic of ANP-vesicles are considered in the discussion. ..
  4. Dai H, Shin O, Machius M, Tomchick D, Sudhof T, Rizo J. Structural basis for the evolutionary inactivation of Ca2+ binding to synaptotagmin 4. Nat Struct Mol Biol. 2004;11:844-9 pubmed
  5. Poopatanapong A, Teramitsu I, Byun J, Vician L, Herschman H, White S. Singing, but not seizure, induces synaptotagmin IV in zebra finch song circuit nuclei. J Neurobiol. 2006;66:1613-29 pubmed
    b>Synaptotagmins are a family of proteins that function in membrane fusion events, including synaptic vesicle exocytosis. Within this family, synaptotagmin IV (Syt IV) is unique in being a depolarization-induced immediate early gene (IEG)...
  6. James D, Kowalchyk J, Daily N, Petrie M, Martin T. CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions. Proc Natl Acad Sci U S A. 2009;106:17308-13 pubmed publisher
    ..The results revealed an unexpected activity of a priming protein to accelerate fusion by efficiently promoting trans-SNARE complex formation. CAPS may function in priming by organizing SNARE complexes on the plasma membrane. ..
  7. Inoue S, Imamura A, Okazaki Y, Yokota H, Arai M, Hayashi N, et al. Synaptotagmin XI as a candidate gene for susceptibility to schizophrenia. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:332-40 pubmed
    ..Another (single nucleotide) polymorphism in the Syt11 5'UTR region, where the potent transcription factor YY1 can bind, also affects the transcriptional activity of Syt11. ..
  8. Jorquera R, Huntwork Rodriguez S, Akbergenova Y, Cho R, Littleton J. Complexin controls spontaneous and evoked neurotransmitter release by regulating the timing and properties of synaptotagmin activity. J Neurosci. 2012;32:18234-45 pubmed publisher
    ..These observations indicate CPX regulates both spontaneous and evoked fusion by modulating the timing and properties of SYT activation during the synaptic vesicle cycle. ..
  9. Hu Z, Chen M, Ping Z, Dong Y, Zhang R, Xu T, et al. Synaptotagmin IV regulates dense core vesicle (DCV) release in LbetaT2 cells. Biochem Biophys Res Commun. 2008;371:781-6 pubmed publisher
    b>Synaptotagmins (Syts) are calcium-binding proteins which are conserved from nematodes to humans. Fifteen Syts have been identified in mammalian species...

More Information


  1. Gauthier B, Duhamel D, Iezzi M, Theander S, Saltel F, Fukuda M, et al. Synaptotagmin VII splice variants alpha, beta, and delta are expressed in pancreatic beta-cells and regulate insulin exocytosis. FASEB J. 2008;22:194-206 pubmed
    b>Synaptotagmins (SYT) are calcium-binding proteins that participate in regulated exocytosis...
  2. Richards D, Bai J, Chapman E. Two modes of exocytosis at hippocampal synapses revealed by rate of FM1-43 efflux from individual vesicles. J Cell Biol. 2005;168:929-39 pubmed
  3. Barber C, Jorquera R, Melom J, Littleton J. Postsynaptic regulation of synaptic plasticity by synaptotagmin 4 requires both C2 domains. J Cell Biol. 2009;187:295-310 pubmed publisher serine 284, an evolutionarily conserved substitution for a key Ca(2+)-binding aspartic acid found in other synaptotagmins. These data suggest that Syt 4 regulates activity-dependent release of postsynaptic retrograde signals that ..
  4. Hui E, Johnson C, Yao J, Dunning F, Chapman E. Synaptotagmin-mediated bending of the target membrane is a critical step in Ca(2+)-regulated fusion. Cell. 2009;138:709-21 pubmed publisher
    ..Moreover, bending of flat membranes by adding an N-BAR domain rescued the function of the tubulation-deficient syt mutant. Hence, syt-mediated membrane bending is a critical step in membrane fusion. ..
  5. Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon P. Synaptotagmin IV regulates glial glutamate release. Proc Natl Acad Sci U S A. 2004;101:9441-6 pubmed
    Calcium-binding synaptotagmins (Syts) are membrane proteins that are conserved from nematode to human. Fifteen Syts (Syts I-XV) have been identified in mammalian species...
  6. Willig K, Rizzoli S, Westphal V, Jahn R, Hell S. STED microscopy reveals that synaptotagmin remains clustered after synaptic vesicle exocytosis. Nature. 2006;440:935-9 pubmed publisher
    ..Our study also demonstrates that questions involving cellular structures with dimensions of a few tens of nanometres can be resolved with conventional far-field optics and visible light...
  7. Kang R, Swayze R, Lise M, Gerrow K, Mullard A, Honer W, et al. Presynaptic trafficking of synaptotagmin I is regulated by protein palmitoylation. J Biol Chem. 2004;279:50524-36 pubmed
    ..We conclude that palmitoylation is involved in trafficking of specific elements involved in transmitter release and that distinct mechanisms regulate addition and removal of palmitate on select neuronal proteins. ..
  8. Pan P, Tian J, Sheng Z. Snapin facilitates the synchronization of synaptic vesicle fusion. Neuron. 2009;61:412-24 pubmed publisher
    ..Our studies provide mechanistic insights into a dual role of Snapin in enhancing the efficacy of SV priming and in fine-tuning synchronous SV fusion. ..
  9. Johnson S, Franz C, Kuhn S, Furness D, Rüttiger L, Münkner S, et al. Synaptotagmin IV determines the linear Ca2+ dependence of vesicle fusion at auditory ribbon synapses. Nat Neurosci. 2010;13:45-52 pubmed publisher
    ..Moreover, the expression of the hitherto undetected synaptotagmins I and II correlated with a high-order Ca(2+) dependence in IHCs...
  10. Iezzi M, Eliasson L, Fukuda M, Wollheim C. Adenovirus-mediated silencing of synaptotagmin 9 inhibits Ca2+-dependent insulin secretion in islets. FEBS Lett. 2005;579:5241-6 pubmed
    b>Synaptotagmins (Syts) are involved in Ca(2+)-dependent insulin release. However, which Syt isoform is functional in primary beta-cells remains unknown...
  11. Arantes R, Andrews N. A role for synaptotagmin VII-regulated exocytosis of lysosomes in neurite outgrowth from primary sympathetic neurons. J Neurosci. 2006;26:4630-7 pubmed
  12. Jaiswal J, Chakrabarti S, Andrews N, Simon S. Synaptotagmin VII restricts fusion pore expansion during lysosomal exocytosis. PLoS Biol. 2004;2:E233 pubmed
    ..These observations indicate that Syt VII does not function as the calcium-dependent trigger for lysosomal exocytosis. Instead, it restricts the kinetics and extent of calcium-dependent lysosomal fusion. ..
  13. Rickman C, Craxton M, Osborne S, Davletov B. Comparative analysis of tandem C2 domains from the mammalian synaptotagmin family. Biochem J. 2004;378:681-6 pubmed
    Intracellular membrane traffic is governed by a conserved set of proteins, including Syts (synaptotagmins). The mammalian Syt family includes 15 isoforms...
  14. Yoshihara M, Adolfsen B, Littleton J. Is synaptotagmin the calcium sensor?. Curr Opin Neurobiol. 2003;13:315-23 pubmed
    ..Biochemical and genetic studies suggest that lipid and SNARE interactions underlie synaptotagmin's ability to mediate the incredible speed of vesicle fusion that is the hallmark of fast synaptic transmission. ..
  15. Zhang Z, Hui E, Chapman E, Jackson M. Regulation of exocytosis and fusion pores by synaptotagmin-effector interactions. Mol Biol Cell. 2010;21:2821-31 pubmed publisher
    ..This associates the syt-PS interaction with two distinct kinetic steps in Ca(2+) triggered exocytosis and supports a role for the syt-PS interaction in stabilizing open fusion pores. ..
  16. Krishnakumar S, Radoff D, Kümmel D, Giraudo C, Li F, Khandan L, et al. A conformational switch in complexin is required for synaptotagmin to trigger synaptic fusion. Nat Struct Mol Biol. 2011;18:934-40 pubmed publisher
  17. Dean C, Liu H, Dunning F, Chang P, Jackson M, Chapman E. Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release. Nat Neurosci. 2009;12:767-76 pubmed publisher
    ..Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP. ..
  18. Xu J, Brewer K, Perez Castillejos R, Rizo J. Subtle Interplay between synaptotagmin and complexin binding to the SNARE complex. J Mol Biol. 2013;425:3461-75 pubmed publisher
  19. Arac D, Chen X, Khant H, Ubach J, Ludtke S, Kikkawa M, et al. Close membrane-membrane proximity induced by Ca(2+)-dependent multivalent binding of synaptotagmin-1 to phospholipids. Nat Struct Mol Biol. 2006;13:209-17 pubmed
    ..We propose a model wherein synaptotagmin cooperates with the SNAREs in bringing the synaptic vesicle and plasma membranes together and accelerates membrane fusion through the highly positive electrostatic potential of its C(2)B domain. ..
  20. Rickman C, Jimenez J, Graham M, Archer D, Soloviev M, Burgoyne R, et al. Conserved prefusion protein assembly in regulated exocytosis. Mol Biol Cell. 2006;17:283-94 pubmed
  21. Fukuda M. Molecular cloning, expression, and characterization of a novel class of synaptotagmin (Syt XIV) conserved from Drosophila to humans. J Biochem. 2003;133:641-9 pubmed
    b>Synaptotagmins (Syts) represent a large family of putative membrane trafficking proteins found in various species from different phyla...
  22. Pawlu C, DiAntonio A, Heckmann M. Postfusional control of quantal current shape. Neuron. 2004;42:607-18 pubmed
    ..Quantal glutamate discharge time course depends on presynaptic calcium inflow and the molecular composition of the release machinery. ..
  23. Segovia M, Ales E, Montes M, Bonifas I, Jemal I, Lindau M, et al. Push-and-pull regulation of the fusion pore by synaptotagmin-7. Proc Natl Acad Sci U S A. 2010;107:19032-7 pubmed publisher
    ..b>Synaptotagmins contain two C2 domains that both bind Ca(2+) and contribute to exocytosis; however, it remains unknown whether ..
  24. Monterrat C, Boal F, Grise F, Hemar A, Lang J. Synaptotagmin 8 is expressed both as a calcium-insensitive soluble and membrane protein in neurons, neuroendocrine and endocrine cells. Biochim Biophys Acta. 2006;1763:73-81 pubmed
    b>Synaptotagmins (syt) form a large family of transmembrane proteins and some of its isoforms are known to regulate calcium-induced membrane fusion during vesicular traffic...
  25. 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 a cofactor for both synaptotagmin-1 and synaptotagmin-10 despite the functional differences between these synaptotagmins. Rescue experiments revealed that only the activating but not the clamping function of complexins was required ..
  26. Sara Y, Virmani T, Deak F, Liu X, Kavalali E. An isolated pool of vesicles recycles at rest and drives spontaneous neurotransmission. Neuron. 2005;45:563-73 pubmed
    ..Taken together these results suggest that spontaneously recycling vesicles and activity-dependent recycling vesicles originate from distinct pools with limited cross-talk with each other. ..
  27. Yoshihara M, Montana E. The synaptotagmins: calcium sensors for vesicular trafficking. Neuroscientist. 2004;10:566-74 pubmed
    ..This suggests an intriguing possibility that syt 4 may mediate a postsynaptic vesicle trafficking pathway, providing a molecular basis for an evolutionarily conserved bidirectional vesicular trafficking communication system at synapses. ..
  28. Cao P, Maximov A, Sudhof T. Activity-dependent IGF-1 exocytosis is controlled by the Ca(2+)-sensor synaptotagmin-10. Cell. 2011;145:300-11 pubmed publisher
    b>Synaptotagmins Syt1, Syt2, Syt7, and Syt9 act as Ca(2+)-sensors for synaptic and neuroendocrine exocytosis, but the function of other synaptotagmins remains unknown...
  29. Matsumoto J, Katsuyama Y, Ohtsuka Y, Lemaire P, Okamura Y. Functional analysis of synaptotagmin gene regulatory regions in two distantly related ascidian species. Dev Growth Differ. 2008;50:543-52 pubmed publisher
    ..The homeodomain binding sites in this region are required for the neuronal enhancer activity. These results suggest that GATA and homeodomain transcription factors regulate the expression of synaptotagmin...
  30. Fukuda M, Kanno E, Satoh M, Saegusa C, Yamamoto A. Synaptotagmin VII is targeted to dense-core vesicles and regulates their Ca2+ -dependent exocytosis in PC12 cells. J Biol Chem. 2004;279:52677-84 pubmed
  31. Gauthier B, Wollheim C. Synaptotagmins bind calcium to release insulin. Am J Physiol Endocrinol Metab. 2008;295:E1279-86 pubmed publisher
    ..Herein, we review the physiological function of the various synaptotagmins with reference to their impact on insulin exocytosis...
  32. Zhang Z, Zhang Z, Jackson M. Synaptotagmin IV modulation of vesicle size and fusion pores in PC12 cells. Biophys J. 2010;98:968-78 pubmed publisher
    Many synaptotagmins are Ca(2+)-binding membrane proteins with functions in Ca(2+)-triggered exocytosis. Synaptotagmin IV (syt IV) has no Ca(2+) binding activity, but nevertheless modulates exocytosis...
  33. Wang P, Wang C, Bai J, Jackson M, Chapman E. Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner. J Biol Chem. 2003;278:47030-7 pubmed
    ..These findings indicate that the tandem C2 domains of syt cooperate with one another to trigger release via loop-mediated electrostatic interactions with effector molecules. ..
  34. Craxton M. Synaptotagmin gene content of the sequenced genomes. BMC Genomics. 2004;5:43 pubmed
    b>Synaptotagmins exist as a large gene family in mammals. There is much interest in the function of certain family members which act crucially in the regulated synaptic vesicle exocytosis required for efficient neurotransmission...
  35. Sudhof T, Rothman J. Membrane fusion: grappling with SNARE and SM proteins. Science. 2009;323:474-7 pubmed publisher
  36. 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. ..
  37. Jahn J, Coleman W. Re-expression of tumorigenicity after attenuation of human synaptotagmin 13 in a suppressed microcell hybrid cell line. Int J Oncol. 2008;32:441-9 pubmed
  38. Glavan G, Zivin M. Differential expression of striatal synaptotagmin mRNA isoforms in hemiparkinsonian rats. Neuroscience. 2005;135:545-54 pubmed
    b>Synaptotagmins (Syts) constitute a multi-gene family of 15 putative membrane trafficking proteins...
  39. Chicka M, Chapman E. Concurrent binding of complexin and synaptotagmin to liposome-embedded SNARE complexes. Biochemistry. 2009;48:657-9 pubmed publisher
    ..These data also suggest that during synaptotagmin-regulated vesicle-vesicle fusion, complexin does not function as a fusion clamp that is relieved by Ca(2+)-synaptotagmin. ..
  40. Ahras M, Otto G, Tooze S. Synaptotagmin IV is necessary for the maturation of secretory granules in PC12 cells. J Cell Biol. 2006;173:241-51 pubmed
    ..Granule formation, and the sorting of SgII and PC2 from the trans-Golgi network into ISGs and MSGs, however, is not affected. We conclude that Syt IV is an essential component for secretory granule maturation. ..
  41. Roy D, Liston D, Idone V, Di A, Nelson D, Pujol C, et al. A process for controlling intracellular bacterial infections induced by membrane injury. Science. 2004;304:1515-8 pubmed
    ..Thus, the lysosomal repair response can also protect cells against pathogens that trigger membrane permeabilization...
  42. Lazzell D, Belizaire R, Thakur P, Sherry D, Janz R. SV2B regulates synaptotagmin 1 by direct interaction. J Biol Chem. 2004;279:52124-31 pubmed publisher
    ..This study has demonstrated a new role of SV2B as a regulator of synaptotagmin 1 that is likely mediated by direct interaction of these two synaptic proteins...
  43. Zhang G, Bai H, Zhang H, Dean C, Wu Q, Li J, et al. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron. 2011;69:523-35 pubmed publisher
    ..In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases. ..
  44. Sagi Eisenberg R. The mast cell: where endocytosis and regulated exocytosis meet. Immunol Rev. 2007;217:292-303 pubmed
    ..These studies have identified synaptotagmins (Syts) II, III, and IX as well as neuronal Ca(2+) sensor 1 (NCS-1) as important regulators of mast cell ..
  45. Loewen C, Lee S, Shin Y, Reist N. C2B polylysine motif of synaptotagmin facilitates a Ca2+-independent stage of synaptic vesicle priming in vivo. Mol Biol Cell. 2006;17:5211-26 pubmed
    ..Together, our results demonstrate that the polylysine motif is required for efficient Ca2+-independent docking and/or priming of synaptic vesicles in vivo. ..
  46. Melia T. Putting the clamps on membrane fusion: how complexin sets the stage for calcium-mediated exocytosis. FEBS Lett. 2007;581:2131-9 pubmed
    ..By arresting vesicle secretion just prior to fusion, complexin primes select vesicles for a fast, synchronous response to calcium. ..
  47. Schapire A, Valpuesta V, Botella M. Plasma membrane repair in plants. Trends Plant Sci. 2009;14:645-52 pubmed publisher
    ..Animal proteins with Ca(2+)-binding domains such as synaptotagmins and dysferlin mediate Ca(2+)-dependent exocytosis to repair plasma membranes after mechanical damage...
  48. 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
  49. Zhu D, Zhou W, Liang T, Yang F, Zhang R, Wu Z, et al. Synaptotagmin I and IX function redundantly in controlling fusion pore of large dense core vesicles. Biochem Biophys Res Commun. 2007;361:922-7 pubmed
    b>Synaptotagmins (Syts) constitute a large family of at least 16 members and individual Syt isoforms exhibit distinct Ca(2+)-binding properties and subcellular localization...
  50. Craxton M. Evolutionary genomics of plant genes encoding N-terminal-TM-C2 domain proteins and the similar FAM62 genes and synaptotagmin genes of metazoans. BMC Genomics. 2007;8:259 pubmed
    ..Genes encoding proteins with N-terminal-transmembrane-C2 domain architectures resembling synaptotagmins, are widespread in eukaryotes. A collection of these genes is presented here...
  51. Jahn R, Lang T, Sudhof T. Membrane fusion. Cell. 2003;112:519-33 pubmed
    ..Cellular fusion machines are adapted to fit the needs of different reactions but operate by similar principles in order to achieve merging of the bilayers. ..
  52. Bowen M, Weninger K, Ernst J, Chu S, Brunger A. Single-molecule studies of synaptotagmin and complexin binding to the SNARE complex. Biophys J. 2005;89:690-702 pubmed
    ..These results demonstrate that single molecule FRET can be used as a "spectroscopic ruler" to simultaneously gain structural and kinetic information about transient multiprotein complexes at the membrane interface. ..
  53. Dasgupta S, Kelly R. Internalization signals in synaptotagmin VII utilizing two independent pathways are masked by intramolecular inhibitions. J Cell Sci. 2003;116:1327-37 pubmed
    ..We propose that endocytosis of synaptotagmin VII is regulated in this way to allow it to couple the processes of regulated exocytosis and compensatory endocytosis. ..