Alternative titles; symbols
HGNC Approved Gene Symbol: ADGRG3
Cytogenetic location: 16q21 Genomic coordinates (GRCh38) : 16:57,665,629-57,689,378 (from NCBI)
ADGRG3 is a transmembrane G protein-coupled receptor (GPCR) that regulates migration of lymphatic endothelial cells (LECs) by controlling activation of the small GTPases RHOA (165390) and CDC42 (116952) (Valtcheva et al., 2013).
Using quantitative RT-PCR, Valtcheva et al. (2013) identified Adgrg3, which they called Gpr97, based on its differential expression in LECs versus blood vascular endothelial cells from mouse intestine. RT-PCR and Western blot analyses showed that GPR97 was expressed at the mRNA and protein levels in cultured primary human LECs.
Valtcheva et al. (2013) found that knockdown of GPR97 in primary human LECs enhanced collective migration compared with control cells and led to faster wound closure independently of matrix components or secreted molecules. Silencing GPR97 in LECs caused redistribution of F-actin and vinculin (VCL; 193065), elevated levels of active CDC42, and decreased levels of active RHOA. Activation of CDC42 enhanced wound closure of control LECs to a similar extent as GPR97 knockdown, whereas activation of RHOA reversed the increased cell migration after GPR97 knockdown to control levels. Despite increased collective cell migration following GPR97 knockdown, single cell migration decreased and adhesion to fibronectin (see 135600) and type I collagen (see 120150) increased in GPR97-deficient LECs compared with control LECs. GPR97-deficient LECs also showed increased activation of beta-1 integrin (ITGB1; 135630), a component of both fibronectin and type I collagen receptors. GPR97-deficient LECs showed slightly increased phosphorylation of PAK4 (605451) and paxillin (PXN; 602505).
Gross (2019) mapped the ADGRG3 gene to chromosome 16q21 based on an alignment of the ADGRG3 sequence (GenBank BC064508) with the genomic sequence (GRCh38).
Gross, M. B. Personal Communication. Baltimore, Md. 5/21/2019.
Valtcheva, N., Primorac, A., Jurisic, G., Hollmen, M., Detmar, M. The orphan adhesion G protein-coupled receptor GPR97 regulates migration of lymphatic endothelial cells via the small GTPases RhoA and Cdc42. J. Biol. Chem. 288: 35736-35748, 2013. [PubMed: 24178298] [Full Text: https://doi.org/10.1074/jbc.M113.512954]