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Gene Review

Syt1  -  synaptotagmin I

Rattus norvegicus

Synonyms: Synaptotagmin I, Synaptotagmin-1, SytI, p65
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Disease relevance of Syt1


Psychiatry related information on Syt1


High impact information on Syt1


Chemical compound and disease context of Syt1


Biological context of Syt1


Anatomical context of Syt1


Associations of Syt1 with chemical compounds

  • The tandem C2 domains of syt cooperate to mediate binding to syntaxin/SNAP-25; lengthening the linker that connects C2A and C2B selectively disrupts this interaction [15].
  • Here we examined the requirement of the C2A polylysine motif for Syt 1 interaction with the cardiac Cav1.2 (L-type) and the neuronal Cav2.3 (R-type) voltage-gated Ca2+ channels, two channels required for neurotransmission [16].
  • Synaptotagmin-I binding is abolished by mutations in two positively charged amino acids in the C(2) domains of RIM and by the addition of inositol polyphosphates [22].
  • Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate [20].
  • Ca(2+) promotes the interaction of syt with anionic phospholipids and the target membrane SNAREs (t-SNAREs) SNAP-25 and syntaxin [23].

Physical interactions of Syt1

  • Binding assays in vitro using recombinant proteins confirmed a direct interaction between the two proteins and demonstrated that the PKA-phosphorylated form of CSP binds synaptotagmin with approximately an order of magnitude lower affinity than the non-phosphorylated form [21].
  • We report that SV2 is part of a large protein complex that contains the synaptic vesicle protein synaptotagmin [24].
  • On the structure of the 'synaptosecretosome'. Evidence for a neurexin/synaptotagmin/syntaxin/Ca2+ channel complex [25].

Enzymatic interactions of Syt1


Co-localisations of Syt1


Regulatory relationships of Syt1


Other interactions of Syt1


Analytical, diagnostic and therapeutic context of Syt1


  1. Functional analysis of the C2A domain of synaptotagmin 1: implications for calcium-regulated secretion. Thomas, D.M., Elferink, L.A. J. Neurosci. (1998) [Pubmed]
  2. Pdx-1 enables insulin secretion by regulating synaptotagmin 1 gene expression. Nakajima-Nagata, N., Sugai, M., Sakurai, T., Miyazaki, J., Tabata, Y., Shimizu, A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  3. Binding of botulinum type B neurotoxin to Chinese hamster ovary cells transfected with rat synaptotagmin II cDNA. Nishiki, T., Tokuyama, Y., Kamata, Y., Nemoto, Y., Yoshida, A., Sekiguchi, M., Takahashi, M., Kozaki, S. Neurosci. Lett. (1996) [Pubmed]
  4. Synaptotagmin can cause an immune-mediated model of Lambert-Eaton myasthenic syndrome in rats. Takamori, M., Hamada, T., Komai, K., Takahashi, M., Yoshida, A. Ann. Neurol. (1994) [Pubmed]
  5. Kinetics of synaptotagmin responses to Ca2+ and assembly with the core SNARE complex onto membranes. Davis, A.F., Bai, J., Fasshauer, D., Wolowick, M.J., Lewis, J.L., Chapman, E.R. Neuron (1999) [Pubmed]
  6. Role of nigral NFkappaB p50 and p65 subunit expression in haloperidol-induced neurotoxicity and stereotyped behavior in rats. Saldaña, M., Bonastre, M., Aguilar, E., Marin, C. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2006) [Pubmed]
  7. Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Reddy, A., Caler, E.V., Andrews, N.W. Cell (2001) [Pubmed]
  8. Structure of the first C2 domain of synaptotagmin I: a novel Ca2+/phospholipid-binding fold. Sutton, R.B., Davletov, B.A., Berghuis, A.M., Südhof, T.C., Sprang, S.R. Cell (1995) [Pubmed]
  9. A role for synaptotagmin (p65) in regulated exocytosis. Elferink, L.A., Peterson, M.R., Scheller, R.H. Cell (1993) [Pubmed]
  10. Non-invasive detection of apoptosis using magnetic resonance imaging and a targeted contrast agent. Zhao, M., Beauregard, D.A., Loizou, L., Davletov, B., Brindle, K.M. Nat. Med. (2001) [Pubmed]
  11. Asbestos causes translocation of p65 protein and increases NF-kappa B DNA binding activity in rat lung epithelial and pleural mesothelial cells. Janssen, Y.M., Driscoll, K.E., Howard, B., Quinlan, T.R., Treadwell, M., Barchowsky, A., Mossman, B.T. Am. J. Pathol. (1997) [Pubmed]
  12. Nuclear factor-kappa B p65 in NMDA-induced retinal neurotoxicity. Kitaoka, Y., Kumai, T., Kitaoka, Y., Lam, T.T., Munemasa, Y., Isenoumi, K., Motoki, M., Kuribayashi, K., Kogo, J., Kobayashi, S., Ueno, S. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  13. Immunohistochemical distribution of activated nuclear factor kappaB and peroxisome proliferator-activated receptors in carbon tetrachloride-induced chronic liver injury in rats. Orfila, C., Lepert, J.C., Alric, L., Carrera, G., Béraud, M., Pipy, B. Histochem. Cell Biol. (2005) [Pubmed]
  14. Synaptotagmin I hypothalamic knockdown prevents amygdaloid seizure-induced damage of hippocampal neurons but not of entorhinal neurons. Kobayashi, S., Ohno, K., Iwakuma, M., Kaneda, Y., Saji, M. Neurosci. Res. (2002) [Pubmed]
  15. Fusion pore dynamics are regulated by synaptotagmin*t-SNARE interactions. Bai, J., Wang, C.T., Richards, D.A., Jackson, M.B., Chapman, E.R. Neuron (2004) [Pubmed]
  16. The C2A domain of synaptotagmin alters the kinetics of voltage-gated Ca2+ channels Ca(v)1.2 (Lc-type) and Ca(v)2.3 (R-type). Cohen, R., Elferink, L.A., Atlas, D. J. Biol. Chem. (2003) [Pubmed]
  17. GAL4-NF-kappaB Fusion Protein Augments Transgene Expression from Neuronal Promoters in the Rat Brain. Liu, B.H., Yang, Y., Paton, J.F., Li, F., Boulaire, J., Kasparov, S., Wang, S. Mol. Ther. (2006) [Pubmed]
  18. Synaptotagmin II. A novel differentially distributed form of synaptotagmin. Geppert, M., Archer, B.T., Südhof, T.C. J. Biol. Chem. (1991) [Pubmed]
  19. Mutations in the effector binding loops in the C2A and C2B domains of synaptotagmin I disrupt exocytosis in a nonadditive manner. Wang, P., Wang, C.T., Bai, J., Jackson, M.B., Chapman, E.R. J. Biol. Chem. (2003) [Pubmed]
  20. Synaptotagmin interaction with the syntaxin/SNAP-25 dimer is mediated by an evolutionarily conserved motif and is sensitive to inositol hexakisphosphate. Rickman, C., Archer, D.A., Meunier, F.A., Craxton, M., Fukuda, M., Burgoyne, R.D., Davletov, B. J. Biol. Chem. (2004) [Pubmed]
  21. Phosphorylation-dependent interaction of the synaptic vesicle proteins cysteine string protein and synaptotagmin I. Evans, G.J., Morgan, A. Biochem. J. (2002) [Pubmed]
  22. Direct interaction of the Rab3 effector RIM with Ca2+ channels, SNAP-25, and synaptotagmin. Coppola, T., Magnin-Luthi, S., Perret-Menoud, V., Gattesco, S., Schiavo, G., Regazzi, R. J. Biol. Chem. (2001) [Pubmed]
  23. Ca(2+)-synaptotagmin directly regulates t-SNARE function during reconstituted membrane fusion. Bhalla, A., Chicka, M.C., Tucker, W.C., Chapman, E.R. Nat. Struct. Mol. Biol. (2006) [Pubmed]
  24. Isoform-specific, calcium-regulated interaction of the synaptic vesicle proteins SV2 and synaptotagmin. Schivell, A.E., Batchelor, R.H., Bajjalieh, S.M. J. Biol. Chem. (1996) [Pubmed]
  25. On the structure of the 'synaptosecretosome'. Evidence for a neurexin/synaptotagmin/syntaxin/Ca2+ channel complex. O'Connor, V.M., Shamotienko, O., Grishin, E., Betz, H. FEBS Lett. (1993) [Pubmed]
  26. Phosphorylation of synaptic vesicle protein 2 modulates binding to synaptotagmin. Pyle, R.A., Schivell, A.E., Hidaka, H., Bajjalieh, S.M. J. Biol. Chem. (2000) [Pubmed]
  27. Synaptotagmin I is present mainly in autonomic and sensory neurons of the rat peripheral nervous system. Li, J.Y., Jahn, R., Dahlström, A. Neuroscience (1994) [Pubmed]
  28. Reconstitution of Ca2+-regulated membrane fusion by synaptotagmin and SNAREs. Tucker, W.C., Weber, T., Chapman, E.R. Science (2004) [Pubmed]
  29. C-terminal ECFP fusion impairs synaptotagmin 1 function: crowding out synaptotagmin 1. Han, W., Rhee, J.S., Maximov, A., Lin, W., Hammer, R.E., Rosenmund, C., Südhof, T.C. J. Biol. Chem. (2005) [Pubmed]
  30. Protein synthesis-dependent and -independent regulation of hippocampal synapses by brain-derived neurotrophic factor. Tartaglia, N., Du, J., Tyler, W.J., Neale, E., Pozzo-Miller, L., Lu, B. J. Biol. Chem. (2001) [Pubmed]
  31. Reinvestigation of the role of snapin in neurotransmitter release. Vites, O., Rhee, J.S., Schwarz, M., Rosenmund, C., Jahn, R. J. Biol. Chem. (2004) [Pubmed]
  32. Transcriptional regulation of major histocompatibility complex class I gene by insulin and IGF-I in FRTL-5 thyroid cells. Giuliani, C., Saji, M., Bucci, I., Fiore, G., Liberatore, M., Singer, D.S., Monaco, F., Kohn, L.D., Napolitano, G. J. Endocrinol. (2006) [Pubmed]
  33. Synaptobrevin 2 is palmitoylated in synaptic vesicles prepared from adult, but not from embryonic brain. Veit, M., Becher, A., Ahnert-Hilger, G. Mol. Cell. Neurosci. (2000) [Pubmed]
  34. Inositol hexakisphosphate (InsP6) can weaken the Ca(2+)-dependent membrane binding of C2AB domain of synaptotagmin I. Lu, Y.J., He, Y., Sui, S.F. FEBS Lett. (2002) [Pubmed]
  35. Regulation of exocytosis through Ca2+/ATP-dependent binding of autophosphorylated Ca2+/calmodulin-activated protein kinase II to syntaxin 1A. Ohyama, A., Hosaka, K., Komiya, Y., Akagawa, K., Yamauchi, E., Taniguchi, H., Sasagawa, N., Kumakura, K., Mochida, S., Yamauchi, T., Igarashi, M. J. Neurosci. (2002) [Pubmed]
  36. Synaptotagmin gene content of the sequenced genomes. Craxton, M. BMC Genomics (2004) [Pubmed]
  37. Developmental regulation of synaptotagmin I, II, III, and IV mRNAs in the rat CNS. Berton, F., Iborra, C., Boudier, J.A., Seagar, M.J., Marquèze, B. J. Neurosci. (1997) [Pubmed]
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