Alternative titles; symbols
HGNC Approved Gene Symbol: LIN7C
Cytogenetic location: 11p14.1 Genomic coordinates (GRCh38): 11:27,494,418-27,506,769 (from NCBI)
By searching EST databases for homologs of C. elegans Lin7, Butz et al. (1998) identified murine Lin7c, which they called Veli3. The deduced 197-amino acid Veli3 protein has a C-terminal PDZ domain.
By Northern blot analysis, Jo et al. (1999) found that rat Lin7c, which they called Mals3, showed highest expression in kidney, followed by brain and liver. Weak expression was detected in thymus and heart, and no expression was detected in spleen. Mals3 had an apparent molecular mass of 25 kD by Western blot analysis.
By immunohistochemistry and in situ hybridization using antibodies and cRNAs specific for mouse Mals1 (LIN7A; 603380), Mals2 (LIN7B; 612331), and Mals3, Misawa et al. (2001) showed that each Mals protein localized to distinct brain regions. The Mals proteins were predominantly expressed in both neuronal cell bodies and neuropil, and they were not detected in most nonneuronal cells in brain.
Butz et al. (1998) identified a complex of 3 proteins in rat brain that had the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion. The 3 proteins were Cask (300172), a protein related to membrane-associated guanylate kinases (MAGUKs); Mint1 (APBA1; 602414), a putative vesicular trafficking protein; and the Velis. Cask, Mint1, and the Velis formed a tight, salt-resistant complex. Butz et al. (1998) determined that the N-terminal domains of Cask, Mint1, and the Velis were involved in complex formation, leaving their C-terminal PDZ domains free to recruit adhesion molecules, receptors, and channels to the complex. Butz et al. (1998) proposed that the tripartite complex acts as a nucleation site for the assembly of proteins involved in synaptic vesicle exocytosis and synaptic junctions.
Jo et al. (1999) found that rat Mals proteins immunoprecipitated with Psd95 (DLG4; 602887) and NMDA receptor-2B (GRIN2B; 138252) from solubilized rat cerebral cortex membranes.
Misawa et al. (2001) found that Mals1 -/- Mals2 -/- double-knockout mice appeared normal and showed normal excitatory synaptic activity in the CA1 region of the hippocampus. Mals3 expression was upregulated in most brain regions of the double-knockout mice, suggesting that Mals3 may compensate for loss of Mals1 and Mals2 expression.
Aartsen et al. (2006) found that Mpp4 -/- mouse retinas showed downregulation of Psd95 and mislocalization of both Psd95 and Veli3 at the photoreceptor presynaptic membrane. They proposed that MPP4 may function as a recruitment factor to organize signal transducers at the photoreceptor synapse.
Onda et al. (2007) found that the expression of LIN7C was downregulated in oral squamous cell carcinomas (OSCC; see 275355) compared with normal oral keratinocytes. Overexpression of LIN7C in OSCC cells resulted in a noninvasive phenotype with elevated beta-catenin (CTNNB1; 116806) expression. In immunodeficient mice, tumor cells expressing LIN7C showed reduced metastases. Onda et al. (2007) concluded that LIN7C in a tumor suppressor that functions in the beta-catenin signaling pathway.
By genomic sequence analysis, Taylor et al. (2006) mapped the LIN7C gene to chromosome 11p14.1.
Aartsen, W. M., Kantardzhieva, A., Klooster, J., van Rossum, A. G. S. H., van de Pavert, S. A., Versteeg, I., Cardozo, B. N., Tonagel, F., Beck, S. C., Tanimoto, N., Seeliger, M. W., Wijnholds, J. Mpp4 recruits Psd95 and Veli3 towards the photoreceptor synapse. Hum. Molec. Genet. 15: 1291-1302, 2006. [PubMed: 16520334] [Full Text: https://doi.org/10.1093/hmg/ddl047]
Butz, S., Okamoto, M., Sudhof, T. C. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94: 773-782, 1998. [PubMed: 9753324] [Full Text: https://doi.org/10.1016/s0092-8674(00)81736-5]
Jo, K., Derin, R., Li, M., Bredt, D. S. Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J. Neurosci. 19: 4189-4199, 1999. [PubMed: 10341223] [Full Text: https://doi.org/10.1523/JNEUROSCI.19-11-04189.1999]
Misawa, H., Kawasaki, Y., Mellor, J., Sweeney, N., Jo, K., Nicoll, R. A., Bredt, D. S. Contrasting localizations of MALS/LIN-7 PDZ proteins in brain and molecular compensation in knockout mice. J. Biol. Chem. 276: 9264-9272, 2001. [PubMed: 11104771] [Full Text: https://doi.org/10.1074/jbc.M009334200]
Onda, T., Uzawa, K., Nakashima, D., Saito, K., Iwadate, Y., Seki, N., Shibahara, T., Tanzawa, H. Lin-7C/VELI3/MALS-3: an essential component in metastasis of human squamous cell carcinoma. Cancer Res. 67: 9643-9648, 2007. [PubMed: 17942893] [Full Text: https://doi.org/10.1158/0008-5472.CAN-07-1911]
Taylor, T. D., Noguchi, H., Totoki, Y., Toyoda, A., Kuroki, Y., Dewar, K., Lloyd, C., Itoh, T., Takeda, T., Kim, D.-W., She, X., Barlow, K. F., and 22 others. Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature 440: 497-500, 2006. [PubMed: 16554811] [Full Text: https://doi.org/10.1038/nature04632]