Modulation of renal tubular cell function by RGS3

The recently discovered family of regulators of G protein signaling (RGS) a ccelerates the intrinsic GTPase activity of certain G alpha subunits, there by terminating G protein signaling. Particularly high mRNA levels of one fa mily member, RGS3, are found in the adult kidney. To establish the temporal and spatial renal expression pattern of RGS3, a polyelonal antiserum was r aised against the COOH terminus of RGS3. Staining of mouse renal tissue at different gestational stages revealed high levels of RGS3 within the develo ping and mature tubular epithelial cells. We tested whether RGS3 can modula te tubular migration, an important aspect of tubular development, in respon se to G protein-mediated signaling. Several mouse intermedullary collecting duet (mIMCD-3) cell lines were generated that expressed RGS3 under the con trol of an inducible promoter. Lysophosphatidic acid (LPA) is a potent chem oattractant that mediates its effects through heterotrimeric G proteins. We found that induction of RGS3 significantly reduced LPA-mediated cell migra tion in RGS3-expressing mIMCD-3 clones, whereas chemotaxis induced by hepat ocyte growth factor remained unaffected by RGS3. Our findings suggest that RGS3 modulates tubular functions during renal development and in the adult kidney.