HGNC Approved Gene Symbol: RGS10
Cytogenetic location: 10q26.11 Genomic coordinates (GRCh38): 10:119,499,817-119,542,719 (from NCBI)
RGS proteins negatively regulate signaling pathways involving 7-transmembrane receptors and heterotrimeric G proteins. See 602189 for background.
Using a yeast 2-hybrid system with a mutationally activated form of rat G-alpha(i3) as the bait, Hunt et al. (1996) isolated HeLa cell cDNAs encoding RGS10. Like all members of the RGS family, the predicted 173-amino acid RGS10 contains a 120-amino acid core domain that is strongly conserved with the yeast Sst2 protein. Northern blot analysis detected an approximately 900-bp RGS10 transcript in HeLa cells, human embryonic kidney 293 cells, and mouse brain.
By microarray analysis, Yang and Li (2007) found that RGS10 was highly expressed in human osteoclastoma. Northern blot analysis confirmed high RGS10 expression in osteoclastoma and detected weaker expression in brain, liver, kidney, and the Hep2 cell line; no expression was detected in other tissues and cell lines examined. Mouse Rgs10 was highly expressed in preosteoclasts and osteoclasts derived from RANKL (TNFSF11; 602642)-stimulated bone marrow-derived monocytes, but it was not expressed in osteoblasts or preosteoblasts.
Using coimmunoprecipitation studies, Hunt et al. (1996) demonstrated that RGS10 associates specifically with the activated forms of the 2 related G protein subunits G-alpha(i3) and G-alpha(z) but fails to interact with the structurally and functionally distinct G-alpha(s) subunit. In vitro assays indicated that RGS10 potently and selectively increases the GTP hydrolytic activity of several G-alpha(i) family members.
Using human T cells silenced for or overexpressing RGS10, Garcia-Bernal et al. (2011) showed that RGS10 inhibited G-alpha-dependent, chemokine-upregulated T-cell adhesion mediated by alpha-4 (ITGA4; 192975)/beta-1 (ITGB1; 135630) and alpha-L (ITGAL; 153370)/beta-2 (ITGB2; 600065) integrins. The data suggested that RGS10 opposes activation by chemokines of the VAV1 (164875)-RAC1 (602048) pathway in T cells, leading to repression of adhesion strengthening mediated by alpha-4/beta-1. RGS10 also limited adhesion-independent cell chemotaxis and activation of CDC42 (116952).
Sierra et al. (2002) determined that the RGS10 gene contains 5 exons and spans 35 kb.
By genomic sequence analysis, Sierra et al. (2002) mapped the RGS10 gene to chromosome 10q26.11. They mapped the mouse Rgs10 gene to chromosome 7 by interspecific backcross mapping.
Yang and Li (2007) obtained Rgs10 -/- mice at the expected mendelian ratio, but they were smaller and had shorter limbs than their wildtype littermates. Growth retardation became apparent during the first or second postnatal week. Histologically, Rgs10 -/- mice exhibited severe osteopetrosis. Disruption of Rgs10 impaired osteoclast differentiation due to the absence of calcium current oscillations and loss of Nfatc1 (600489) expression. Ectopic expression of Rgs10 markedly enhanced Rankl-induced osteoclast differentiation. Rgs10 competitively bound Ca(2+)/calmodulin (see CALM1; 114180) and phosphatidylinositol 3-phosphate in a Ca(2+)-dependent manner. Yang and Li (2007) concluded that RGS10 is a key regulator of Ca(2+) current oscillations during osteoclast differentiation.
Garcia-Bernal, D., Dios-Esponera, A., Sotillo-Mallo, E., Garcia-Verdugo, R., Arellano-Sanchez, N., Teixido, J. RGS10 restricts upregulation by chemokines of T cell adhesion mediated by alpha-4-beta-1 and alpha-L-beta-2 integrins. J. Immun. 187: 1264-1272, 2011. [PubMed: 21705617] [Full Text: https://doi.org/10.4049/jimmunol.1002960]
Hunt, T. W., Fields, T. A., Casey, P. J., Peralta, E. G. RGS10 is a selective activator of G-alpha(i) GTPase activity. Nature 383: 175-177, 1996. [PubMed: 8774883] [Full Text: https://doi.org/10.1038/383175a0]
Sierra, D. A., Gilbert, D. J., Householder, D., Grishin, N. V., Yu, K., Ukidwe, P., Barker, S. A., He, W., Wensel, T. G., Otero, G., Brown, G., Copeland, N. G., Jenkins, N. A., Wilkie, T. M. Evolution of the regulators of G-protein signaling multigene family in mouse and human. Genomics 79: 177-185, 2002. [PubMed: 11829488] [Full Text: https://doi.org/10.1006/geno.2002.6693]
Yang, S., Li, Y.-P. RGS10-null mutation impairs osteoclast differentiation resulting from the loss of [Ca2+]i oscillation regulation. Genes Dev. 21: 1803-1816, 2007. [PubMed: 17626792] [Full Text: https://doi.org/10.1101/gad.1544107]