Translocation of Na(+),K(+)-ATPase is induced by Rho small GTPase in renal epithelial cells.
The distribution of transmembrane proteins is considered to be crucial for their activities because these proteins mediate the information coming from outside of cells. A small GTPase Rho participates in many cellular functions through its downstream effectors. In this study, we examined the effects of RhoA on the distribution of Na(+),K(+)-ATPase, one of the transmembrane proteins. In polarized renal epithelium, Na(+),K(+)-ATPase is known to be localized at the basolateral membrane. By microinjection of the constitutively active mutant of RhoA (RhoA(Val14)) into cultured renal epithelial cells, Na(+),K(+)-ATPase was translocated to the spike-like protrusions over the apical surfaces. Microinjection of the constitutively active mutant of other Rho family GTPases, Rac1 or Cdcd42, did not induce the translocation. The translocation induced by RhoA(Val14) was inhibited by treatment with Y-27632, a Rho-kinase specific inhibitor, or by coinjection of the dominant negative mutant of Rho-kinase. These results indicate that Rho and Rho-kinase are involved in the regulation of the localization of Na(+),K(+)-ATPase. We also found that Na(+),K(+)-ATPase seemed to be colocalized with ERM proteins phosphorylated at T567 (ezrin), T564 (radixin), and T558 (moesin) in cells microinjected with RhoA(Val14).
Maeda
Akio
A
Department of Cell Pharmacology, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa, Nagoya, 466-8550, Aichi, Japan.
Amano
Mutsuki
M
Fukata
Yuko
Y
Kaibuchi
Kozo
K
D000577:Amides / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology*; D005799:Genes, Dominant; D005982:Glutathione Transferase / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D018613:Microscopy, Confocal; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D000577:Amides; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D005982:Glutathione Transferase; D020741:rho GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase