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Gene Review

Ss18  -  synovial sarcoma translocation, Chromosome 18

Mus musculus

Synonyms: D130059H17, Protein SSXT, Protein SYT, Ssxt, Synovial sarcoma-associated Ss18-alpha, ...
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Disease relevance of Ss18

  • Isolation and characterization of the mouse homolog of SYT, a gene implicated in the development of human synovial sarcomas [1].

High impact information on Ss18

  • Lysosomal exocytosis and membrane resealing are inhibited by the recombinant Syt VII C(2)A domain or anti-Syt VII C(2)A antibodies, or by antibodies against the cytosolic domain of Lamp-1, which specifically aggregate lysosomes [2].
  • Here, we show that embryonic fibroblasts from Syt VII-deficient mice are less susceptible to trypanosome invasion, and defective in lysosomal exocytosis and resealing after wounding [3].
  • Additional interbreeding of Ss18 and Ss18l1 (Crest) mutant mice indicates that these two functionally and structurally related genes may act synergistically during critical stages of embryonic development [4].
  • Here, we report that disruption of the mouse Ss18 gene results in a recessive embryonic lethal phenotype, due to placental failure caused by impairment of placental vascularization and/or chorio-allantoic fusion [4].
  • Synaptotagmin I (Syt I), an evolutionarily conserved integral membrane protein of synaptic vesicles, is now known to regulate Ca2+-dependent neurotransmitter release [5].

Biological context of Ss18

  • In addition, we identified a mouse Ss18 processed pseudogene and mapped it to chromosome 1, band A2-3 [6].
  • The mouse Ss18 gene, which is subject to extensive alternative splicing, is made up of 11 exons, spread out over approximately 45 kb of genomic sequence [6].
  • The SYT gene was found to be well conserved during evolution and is part of a region of synteny between the human and mouse chromosomes 18 [1].
  • Tissue microarray profiling of primary and xenotransplanted synovial sarcomas demonstrates the immunophenotypic similarities existing between SYT-SSX fusion gene confirmed, biphasic, and monophasic fibrous variants [7].
  • Common post-translational modification(s) of Syt I conserved across phylogeny, however, have never been elucidated [5].

Anatomical context of Ss18

  • Synaptotagmin I (Syt I), a proposed major Ca(2+) sensor in the central nervous system, has been hypothesized as functioning in an oligomerized state during neurotransmitter release [8].
  • 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 [9].
  • Detection of fluorescence protein-tagged Syt IV (Syt IV-EGFP) in hippocampal neurons also showed the presence of Syt IV-EGFP vesicles or organelles in the axons and dendrites [10].
  • By contrast, no staining of either photoreceptor or protein kinase C (PKC)-labeled bipolar cell terminals was detected in the goldfish retina with any of the Syt I/II antibodies [11].
  • We compared secretion from chromaffin cells from Syt1 null mice overexpressing either Syt isoform [12].

Associations of Ss18 with chemical compounds

  • We found that Syt VII is a unique class of synaptotagmins that only showed robust Ca(2+)-dependent self-oligomerization at the cytoplasmic domain with EC(50) values of about 150 micrometer Ca(2+) [13].
  • The former was found to be mediated by a post-translationally modified (i.e. fatty-acylated) cysteine (Cys) cluster (Cys-74, Cys-75, Cys-77, Cys-79, and Cys-82) at the interface between the transmembrane and spacer domains of Syt I [8].
  • Synaptotagmin I (Syt I), a possible Ca(2+) sensor for neurotransmitter release, showed both Ca(2+)-dependent (via the C2 domain) and -independent (via the NH(2)-terminal domain) self-oligomerization, which are thought to be important for synaptic vesicle exocytosis [13].

Analytical, diagnostic and therapeutic context of Ss18


  1. Isolation and characterization of the mouse homolog of SYT, a gene implicated in the development of human synovial sarcomas. de Bruijn, D.R., Baats, E., Zechner, U., de Leeuw, B., Balemans, M., Olde Weghuis, D., Hirning-Folz, U., Geurts van Kessel, A.G. Oncogene (1996) [Pubmed]
  2. Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Reddy, A., Caler, E.V., Andrews, N.W. Cell (2001) [Pubmed]
  3. Impaired membrane resealing and autoimmune myositis in synaptotagmin VII-deficient mice. Chakrabarti, S., Kobayashi, K.S., Flavell, R.A., Marks, C.B., Miyake, K., Liston, D.R., Fowler, K.T., Gorelick, F.S., Andrews, N.W. J. Cell Biol. (2003) [Pubmed]
  4. Targeted disruption of the synovial sarcoma-associated SS18 gene causes early embryonic lethality and affects PPARBP expression. de Bruijn, D.R., Peters, W.J., Chuva de Sousa Lopes, S.M., van Dijk, A.H., Willemse, M.P., Pfundt, R., de Boer, P., Geurts van Kessel, A. Hum. Mol. Genet. (2006) [Pubmed]
  5. Vesicle-associated membrane protein-2/synaptobrevin binding to synaptotagmin I promotes O-glycosylation of synaptotagmin I. Fukuda, M. J. Biol. Chem. (2002) [Pubmed]
  6. Mapping and characterization of the mouse and human SS18 genes, two human SS18-like genes and a mouse Ss18 pseudogene. de Bruijn, D.R., Kater-Baats, E., Eleveld, M., Merkx, G., Geurts Van Kessel, A. Cytogenet. Cell Genet. (2001) [Pubmed]
  7. Tissue microarray profiling of primary and xenotransplanted synovial sarcomas demonstrates the immunophenotypic similarities existing between SYT-SSX fusion gene confirmed, biphasic, and monophasic fibrous variants. Subramaniam, M.M., Navarro, S., Pellin, A., López-Guerrero, J.A., Carda, C., Heredia Alvaro, J.A., Gozalbo Sabater, P.L., Llombart-Bosch, A. Virchows Arch. (2006) [Pubmed]
  8. Mechanism of the SDS-resistant synaptotagmin clustering mediated by the cysteine cluster at the interface between the transmembrane and spacer domains. Fukuda, M., Kanno, E., Ogata, Y., Mikoshiba, K. J. Biol. Chem. (2001) [Pubmed]
  9. 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]
  10. Non-polarized distribution of synaptotagmin IV in neurons: evidence that synaptotagmin IV is not a synaptic vesicle protein. Ibata, K., Hashikawa, T., Tsuboi, T., Terakawa, S., Liang, F., Mizutani, A., Fukuda, M., Mikoshiba, K. Neurosci. Res. (2002) [Pubmed]
  11. 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]
  12. 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]
  13. Distinct self-oligomerization activities of synaptotagmin family. Unique calcium-dependent oligomerization properties of synaptotagmin VII. Fukuda, M., Mikoshiba, K. J. Biol. Chem. (2000) [Pubmed]
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