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SYT7  -  synaptotagmin VII

Homo sapiens

Synonyms: IPCA-7, IPCA7, MGC150517, PCANAP7, Prostate cancer-associated protein 7, ...
 
 
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Disease relevance of SYT7

  • Antibodies against the C(2)A domain of Syt VII or recombinant peptides including this domain inhibit cell entry by T. cruzi, but not by Toxoplasma gondii or Salmonella typhimurium [1].
 

High impact information on SYT7

  • There's more to life than neurotransmission: the regulation of exocytosis by synaptotagmin VII [2].
  • Conversely, HIP14 is catalytically invariant toward paralemmin and synaptotagmin VII [3].
  • The calcium-binding loops of the tandem C2 domains of synaptotagmin VII cooperatively mediate calcium-dependent oligomerization [4].
  • Expression of wild-type tandem C2 domains of Syt VII in PC12 cells inhibited Ca2+-dependent neuropeptide Y release, whereas mutant fragments lacking Ca2+-dependent oligomerization activity had no effect [4].
  • In this study, site-directed mutagenesis and chimeric analysis between Syt I and Syt VII showed that three Asp residues in Ca2+-binding loop 1 or 3 (Asp-172, Asp-303, and Asp-357) are crucial to robust Ca(2+)-dependent oligomerization [4].
 

Biological context of SYT7

  • The investigation of alternatively included exons in CFTR, PER3, CARS and SYT7 supported this finding [5].
  • Synaptotagmin VII (Syt VII) has been proposed to regulate several different types of Ca2+-dependent exocytosis, but its subcellular localization (lysosome or plasma membrane) and the number of alternative splicing isoforms of Syt VII (single or multiple forms) are matters of controversy [6].
  • Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human [6].
  • High-resolution mapping of 34 ESTs binned to the 11q12-q13 region by the Human Transcript Mapping Project identified 5 present in the PAC contig, with 1 of these ESTs identifying a human homologue of the rat synaptotagmin VII gene [7].
  • Recent observations in synaptotagmin-VII-deficient mice suggest that defective membrane repair could lead to autoimmunity in tissues that are more susceptible to mechanical injury [8].
 

Anatomical context of SYT7

  • It was also shown that FLAG-Syt VII-green-fluorescence-protein fusion protein stably expressed in PC12 cells is localized in the perinuclear region (co-localization with TGN38 protein, even after brefeldin A treatment) and in the tips of neurites (co-localization with Syt I), and not in the plasma membrane [6].
  • Here we show that synaptotagmin VII (Syt VII), a ubiquitously expressed synaptotagmin isoform that regulates exocytosis of lysosomes, is localized on the membranes of intracellular vacuoles containing T. cruzi [1].
 

Associations of SYT7 with chemical compounds

  • Ca(2+) entry inevitably follows membrane rupture and recent studies indicate that this elicits repair via Ca(2+)-activated exocytosis of lysosomes, regulated by lysosomal synaptotagmin VII [9].
  • Furthermore, potential target genes of cAMP response element-binding (CREB) protein and/or AP-1 transcription complex, including dynorphin, neogenin, and synaptotagmin VII, are also oppositely regulated by D1 and D3 receptors after repeated cocaine injections [10].
 

Other interactions of SYT7

  • Unlike Syt I, however, the polybasic sequence in the beta4 strands of the C2 structures (so-called "C2 effector domain") is not involved in the Ca2+-dependent oligomerization of Syt VII [4].
 

Analytical, diagnostic and therapeutic context of SYT7

  • Finally, rotary-shadowing electron microscopy showed that the Ca2+-dependent oligomer of Syt VII is "a large linear structure," not an irregular aggregate [4].

References

  1. The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi. Caler, E.V., Chakrabarti, S., Fowler, K.T., Rao, S., Andrews, N.W. J. Exp. Med. (2001) [Pubmed]
  2. There's more to life than neurotransmission: the regulation of exocytosis by synaptotagmin VII. Andrews, N.W., Chakrabarti, S. Trends Cell Biol. (2005) [Pubmed]
  3. Huntingtin-interacting protein HIP14 is a palmitoyl transferase involved in palmitoylation and trafficking of multiple neuronal proteins. Huang, K., Yanai, A., Kang, R., Arstikaitis, P., Singaraja, R.R., Metzler, M., Mullard, A., Haigh, B., Gauthier-Campbell, C., Gutekunst, C.A., Hayden, M.R., El-Husseini, A. Neuron (2004) [Pubmed]
  4. The calcium-binding loops of the tandem C2 domains of synaptotagmin VII cooperatively mediate calcium-dependent oligomerization. Fukuda, M., Katayama, E., Mikoshiba, K. J. Biol. Chem. (2002) [Pubmed]
  5. In NF1, CFTR, PER3, CARS and SYT7, alternatively included exons show higher conservation of surrounding intron sequences than constitutive exons. Kaufmann, D., Kenner, O., Nurnberg, P., Vogel, W., Bartelt, B. Eur. J. Hum. Genet. (2004) [Pubmed]
  6. Alternative splicing isoforms of synaptotagmin VII in the mouse, rat and human. Fukuda, M., Ogata, Y., Saegusa, C., Kanno, E., Mikoshiba, K. Biochem. J. (2002) [Pubmed]
  7. Transcript mapping of the human chromosome 11q12-q13.1 gene-rich region identifies several newly described conserved genes. Cooper, P.R., Nowak, N.J., Higgins, M.J., Church, D.M., Shows, T.B. Genomics (1998) [Pubmed]
  8. Membrane repair and immunological danger. Andrews, N.W. EMBO Rep. (2005) [Pubmed]
  9. Membrane repair: Ca(2+)-elicited lysosomal exocytosis. Gerasimenko, J.V., Gerasimenko, O.V., Petersen, O.H. Curr. Biol. (2001) [Pubmed]
  10. Opposite regulation of cocaine-induced intracellular signaling and gene expression by dopamine d1 and d3 receptors. Zhang, J., Xu, M. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
 
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