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Gene Review

Syt1  -  synaptotagmin I

Mus musculus

Synonyms: AW124717, G630098F17Rik, Synaptotagmin I, Synaptotagmin-1, SytI, ...
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Disease relevance of Syt1

  • The data provide direct evidence for the central importance of p65 in chronic intestinal inflammation and suggest a potential therapeutic utility of p65 antisense oligonucleotides as a novel molecular approach for the treatment of patients with Crohn's disease [1].
  • An infrequent (2-3%) B lymphocyte subpopulation was found in the normal human tonsil and lymph nodes that shows the phenotypic characteristics of B-chronic lymphocytic leukemia (B-CLL) (rosette formation with mouse erythrocytes, weak expression of membrane Ig, staining for HLA-DR, and OKT1 or Leu-1 detecting a T cell-associated p65 antigen) [2].
  • In 2 variations of the model an antisense oligonucleotide for nuclear factor kappa B (NF-kappa B) p65 was given prophylactically or therapeutically to block chronic inflammation-associated fibrosis [3].
  • The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen [4].
  • Conversely, activation of the mouse mammary tumor virus promoter by a combination of dexamethasone and glucocorticoid receptor is inhibited by overexpression of p65 [5].

Psychiatry related information on Syt1

  • Consistent with the idea that the Syt IV mutation preferentially affects hippocampal function, Syt IV mutant mice also display impaired social transmission of food preference [6].

High impact information on Syt1

  • KIF1A was associated with organelles that contained synaptic vesicle proteins such as synaptotagmin, synaptophysin, and Rab3A [7].
  • When introduced by homologous recombination into the endogenous synaptotagmin I gene in mice, this point mutation decreases the Ca2+ sensitivity of neurotransmitter release twofold, but does not alter spontaneous release or the size of the readily releasable pool of neurotransmitters [8].
  • Here we report the crystal structure at 2.9 A resolution of the p50/p65 heterodimer bound to the kappaB DNA of the intronic enhancer of the immunoglobulin light-chain gene [9].
  • The NF-kappaB family members p65 (RelA) and c-Rel recognize similar DNA sequences, yet the phenotypes of mutant mice suggest that these proteins regulate distinct sets of genes [10].
  • Overexpression of p65 increases endogenous I kappa B protein in both carcinoma and lymphoid cells by two mechanisms: protein stabilization and increased transcription of I kappa B mRNA [11].

Chemical compound and disease context of Syt1

  • Molecular basis of complement resistance of human melanoma cells expressing the C3-cleaving membrane protease p65 [12].
  • We examined the effect of antisense oligonucleotides to the p65 subunit of NF-kappaB on the survival of bleomycin (BLM)-induced pneumonitis in C57BL/6 mice (female, 8 wk of age, 17 to 20 g body weight) [13].
  • The effect of intracolonically administered NF-kappaB (p65) antisense phosphorothioate oligonucleotide was examined in mouse DSS-induced colitis using drinking water containing 5% DSS [14].
  • These findings suggest that the suppression of cytokines and mediators in monocytes and alveolar macrophages by the antisense oligonucleotide to the p65 subunit of NF-kappaB worsens the survival of LPS-induced ARDS in mice with the progress of hemorrhagic lung edema [15].
  • To investigate which viral proteinase may be responsible for generating p72 and p65, we expressed the 5'-region of the MHV-JHM RNA polymerase gene including the two papain-like cysteine proteinase domains in an in vitro transcription/translation system and analyzed the translation products for proteolytic processing [16].

Biological context of Syt1


Anatomical context of Syt1


Associations of Syt1 with chemical compounds

  • Synaptotagmin (Syt) I (or II) is thought to be a Ca(2+) sensor for neurotransmitter release in the rostral (or caudal) region of the mammalian brain [18].
  • The developmental expression of synaptotagmin 1, a well characterized glycoprotein of synaptic vesicle, was determined by immunoblots analysis [22].
  • Rabphilin 3A, another neuronal protein containing C2 domains, cannot bind IP4, indicating that the IP4 binding property is specific to the C2B domain of synaptotagmin [23].
  • We now show that in cultured cortical neurons stimulated at low frequency (<or.1 Hz), deletion of synaptotagmin 1 blocks synchronous GABA and glutamate release without significantly increasing asynchronous release [24].
  • Ca(2+) induces binding of the synaptotagmin C(2) domains to SNARE proteins, whereas Sr(2+) even at high concentrations does not [25].

Physical interactions of Syt1

  • Biochemical experiments showed that Syt2 has a slightly lower Ca2+ affinity for phospholipid binding than Syt1 because of a difference in the C2A domain [17].
  • We found that Stx2 binds to Syt I, VI, and VIII in a calcium-dependent manner with EC(50) values of 175, 233, and 96 mum calcium, respectively [19].

Other interactions of Syt1


Analytical, diagnostic and therapeutic context of Syt1


  1. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Neurath, M.F., Pettersson, S., Meyer zum Büschenfelde, K.H., Strober, W. Nat. Med. (1996) [Pubmed]
  2. Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia. Caligaris-Cappio, F., Gobbi, M., Bofill, M., Janossy, G. J. Exp. Med. (1982) [Pubmed]
  3. A murine model of chronic inflammation-induced intestinal fibrosis down-regulated by antisense NF-kappa B. Lawrance, I.C., Wu, F., Leite, A.Z., Willis, J., West, G.A., Fiocchi, C., Chakravarti, S. Gastroenterology (2003) [Pubmed]
  4. The synaptic vesicle protein synaptotagmin associates with calcium channels and is a putative Lambert-Eaton myasthenic syndrome antigen. Leveque, C., Hoshino, T., David, P., Shoji-Kasai, Y., Leys, K., Omori, A., Lang, B., el Far, O., Sato, K., Martin-Moutot, N. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  5. Physical association and functional antagonism between the p65 subunit of transcription factor NF-kappa B and the glucocorticoid receptor. Ray, A., Prefontaine, K.E. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. Deficits in memory and motor performance in synaptotagmin IV mutant mice. Ferguson, G.D., Anagnostaras, S.G., Silva, A.J., Herschman, H.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  7. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Okada, Y., Yamazaki, H., Sekine-Aizawa, Y., Hirokawa, N. Cell (1995) [Pubmed]
  8. Synaptotagmin I functions as a calcium regulator of release probability. Fernández-Chacón, R., Königstorfer, A., Gerber, S.H., García, J., Matos, M.F., Stevens, C.F., Brose, N., Rizo, J., Rosenmund, C., Südhof, T.C. Nature (2001) [Pubmed]
  9. Crystal structure of p50/p65 heterodimer of transcription factor NF-kappaB bound to DNA. Chen, F.E., Huang, D.B., Chen, Y.Q., Ghosh, G. Nature (1998) [Pubmed]
  10. A c-Rel subdomain responsible for enhanced DNA-binding affinity and selective gene activation. Sanjabi, S., Williams, K.J., Saccani, S., Zhou, L., Hoffmann, A., Ghosh, G., Gerondakis, S., Natoli, G., Smale, S.T. Genes Dev. (2005) [Pubmed]
  11. The p65 subunit of NF-kappa B regulates I kappa B by two distinct mechanisms. Scott, M.L., Fujita, T., Liou, H.C., Nolan, G.P., Baltimore, D. Genes Dev. (1993) [Pubmed]
  12. Molecular basis of complement resistance of human melanoma cells expressing the C3-cleaving membrane protease p65. Ollert, M.W., Kadlec, J.V., Petrella, E.C., Bredehorst, R., Vogel, C.W. Cancer Res. (1993) [Pubmed]
  13. Antisense oligonucleotides to NF-kappaB improve survival in bleomycin-induced pneumopathy of the mouse. Zhang, X.Y., Shimura, S., Masuda, T., Saitoh, H., Shirato, K. Am. J. Respir. Crit. Care Med. (2000) [Pubmed]
  14. Therapeutic effect of intracolonically administered nuclear factor kappa B (p65) antisense oligonucleotide on mouse dextran sulphate sodium (DSS)-induced colitis. Murano, M., Maemura, K., Hirata, I., Toshina, K., Nishikawa, T., Hamamoto, N., Sasaki, S., Saitoh, O., Katsu, K. Clin. Exp. Immunol. (2000) [Pubmed]
  15. Effect of antisense oligonucleotides to nuclear factor-kappaB on the survival of LPS-induced ARDS in mouse. Saitoh, H., Masuda, T., Zhang, X.Y., Shimura, S., Shirato, K. Exp. Lung Res. (2002) [Pubmed]
  16. Identification of the polymerase polyprotein products p72 and p65 of the murine coronavirus MHV-JHM. Gao, H.Q., Schiller, J.J., Baker, S.C. Virus Res. (1996) [Pubmed]
  17. Different effects on fast exocytosis induced by synaptotagmin 1 and 2 isoforms and abundance but not by phosphorylation. Nagy, G., Kim, J.H., Pang, Z.P., Matti, U., Rettig, J., Südhof, T.C., Sørensen, J.B. J. Neurosci. (2006) [Pubmed]
  18. Genomic structures of synaptotagmin II protein: comparison of exon-intron organization of the synaptotagmin gene family. Fukuda, M., Mikoshiba, K. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  19. Synaptotagmin VI and VIII and syntaxin 2 are essential for the mouse sperm acrosome reaction. Hutt, D.M., Baltz, J.M., Ngsee, J.K. J. Biol. Chem. (2005) [Pubmed]
  20. Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release. Pang, Z.P., Sun, J., Rizo, J., Maximov, A., Südhof, T.C. EMBO J. (2006) [Pubmed]
  21. The extravesicular domain of synaptotagmin-1 is released with the latent fibroblast growth factor-1 homodimer in response to heat shock. Tarantini, F., LaVallee, T., Jackson, A., Gamble, S., Mouta Carreira, C., Garfinkel, S., Burgess, W.H., Maciag, T. J. Biol. Chem. (1998) [Pubmed]
  22. Synaptic vesicle and synaptic membrane glycoproteins during pre- and postnatal development of mouse cerebral cortex, cerebellum and spinal cord. Mayanil, C.S., Knepper, P.A. Dev. Neurosci. (1993) [Pubmed]
  23. Inositol-1,3,4,5-tetrakisphosphate binding to C2B domain of IP4BP/synaptotagmin II. Fukuda, M., Aruga, J., Niinobe, M., Aimoto, S., Mikoshiba, K. J. Biol. Chem. (1994) [Pubmed]
  24. Autonomous function of synaptotagmin 1 in triggering synchronous release independent of asynchronous release. Maximov, A., Südhof, T.C. Neuron (2005) [Pubmed]
  25. Sr2+ binding to the Ca2+ binding site of the synaptotagmin 1 C2B domain triggers fast exocytosis without stimulating SNARE interactions. Shin, O.H., Rhee, J.S., Tang, J., Sugita, S., Rosenmund, C., Südhof, T.C. Neuron (2003) [Pubmed]
  26. Distribution of the presynaptic calcium sensors, synaptotagmin I/II and synaptotagmin III, in the goldfish and rodent retinas. Berntson, A.K., Morgans, C.W. Journal of vision [electronic resource]. (2003) [Pubmed]
  27. SNAP-25 and synaptotagmin 1 function in Ca2+-dependent reversible docking of granules to the plasma membrane. Chieregatti, E., Witkin, J.W., Baldini, G. Traffic (2002) [Pubmed]
  28. The role of Snapin in neurosecretion: snapin knock-out mice exhibit impaired calcium-dependent exocytosis of large dense-core vesicles in chromaffin cells. Tian, J.H., Wu, Z.X., Unzicker, M., Lu, L., Cai, Q., Li, C., Schirra, C., Matti, U., Stevens, D., Deng, C., Rettig, J., Sheng, Z.H. J. Neurosci. (2005) [Pubmed]
  29. Central pore residues mediate the p97/VCP activity required for ERAD. DeLaBarre, B., Christianson, J.C., Kopito, R.R., Brunger, A.T. Mol. Cell (2006) [Pubmed]
  30. Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I. Nicholson-Tomishima, K., Ryan, T.A. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  31. Comparison of immunolocalization patterns for the synaptic vesicle proteins p65 and synapsin I in macaque monkey retina. Koontz, M.A., Hendrickson, A.E. Synapse (1993) [Pubmed]
  32. Failure of lymphopoiesis after adoptive transfer of NF-kappaB-deficient fetal liver cells. Horwitz, B.H., Scott, M.L., Cherry, S.R., Bronson, R.T., Baltimore, D. Immunity (1997) [Pubmed]
  33. Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation. Nickols, J.C., Valentine, W., Kanwal, S., Carter, B.D. Nat. Neurosci. (2003) [Pubmed]
  34. Organ-specific roles for transcription factor NF-kappaB in reovirus-induced apoptosis and disease. O'Donnell, S.M., Hansberger, M.W., Connolly, J.L., Chappell, J.D., Watson, M.J., Pierce, J.M., Wetzel, J.D., Han, W., Barton, E.S., Forrest, J.C., Valyi-Nagy, T., Yull, F.E., Blackwell, T.S., Rottman, J.N., Sherry, B., Dermody, T.S. J. Clin. Invest. (2005) [Pubmed]
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