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

• Nonetheless, reverse-transcriptase-polymerase chain reaction detected SYT-SSX transcripts in all primary SSs and their xenografts, thereby demonstrating their genetic stability [7].

References