TY - JOUR
T1 - Modulation of renal tubular cell function by RGS3
AU - Grüning, W.
AU - Arnould, T.
AU - Jochimsen, F.
AU - Sellin, L.
AU - Ananth, S.
AU - Kim, E.
AU - Walz, G.
PY - 1999
Y1 - 1999
N2 - The recently discovered family of regulators of G protein signaling (RGS) accelerates the intrinsic GTPase activity of certain Gα subunits, thereby terminating G protein signaling. Particularly high mRNA levels of one family member, RGS3, are found in the adult kidney. To establish the temporal and spatial renal expression pattern of RGS3, a polyclona] antiserum was raised against the COOH terminus of RGS3. Staining of mouse renal tissue at different gestational stages revealed high levels of RGS3 within the developing and mature tubular epithelial cells. We tested whether RGS3 can modulate tubular migration, an important aspect of tubular development, in response to G protein-mediated signaling. Several mouse intermedullary collecting duct (mIMCD-3) cell lines were generated that expressed RGS3 under the control of an inducible promoter, Lysophosphatidic acid (LPA) is a potent chemoattractant that mediates its effects through heterotrimeric G proteins. We found that induction of RGS3 significantly reduced LPA-mediated cell migration in RGS3-expressing mIMCD-3 clones, whereas chemotaxis induced by hepatocyte growth factor remained unaffected by RGS3. Our findings suggest that RGS3 modulates tubular functions during renal development and in the adult kidney.
AB - The recently discovered family of regulators of G protein signaling (RGS) accelerates the intrinsic GTPase activity of certain Gα subunits, thereby terminating G protein signaling. Particularly high mRNA levels of one family member, RGS3, are found in the adult kidney. To establish the temporal and spatial renal expression pattern of RGS3, a polyclona] antiserum was raised against the COOH terminus of RGS3. Staining of mouse renal tissue at different gestational stages revealed high levels of RGS3 within the developing and mature tubular epithelial cells. We tested whether RGS3 can modulate tubular migration, an important aspect of tubular development, in response to G protein-mediated signaling. Several mouse intermedullary collecting duct (mIMCD-3) cell lines were generated that expressed RGS3 under the control of an inducible promoter, Lysophosphatidic acid (LPA) is a potent chemoattractant that mediates its effects through heterotrimeric G proteins. We found that induction of RGS3 significantly reduced LPA-mediated cell migration in RGS3-expressing mIMCD-3 clones, whereas chemotaxis induced by hepatocyte growth factor remained unaffected by RGS3. Our findings suggest that RGS3 modulates tubular functions during renal development and in the adult kidney.
KW - Chemotaxis
KW - G protein
KW - Kidney development
KW - Regulators of G protein signaling
KW - Renal tubular epithelial cells
UR - http://www.scopus.com/inward/record.url?scp=0032957837&partnerID=8YFLogxK
M3 - Article
C2 - 10198412
SN - 1931-857X
VL - 276
SP - F535-543
JO - American Journal of Physiology - Renal Physiology
JF - American Journal of Physiology - Renal Physiology
IS - 4 45-4
ER -