Nongastric H+,K+-ATPase: cell biologic and functional properties.
Several members of the H+,K+-ATPase family of ion pumps participate in renal K transport. This class of P-type ATPases includes the gastric H+,K+-ATPase as well as a number of nongastric H+,K+-ATPase isoforms. Physiological studies suggest that these enzymes operate predominantly at the apical surfaces of tubule epithelial cells. Although much has been learned about the pattern of H+,K+-ATPase isoform expression and its response to stress, the functional and cell biologic attributes of these pumps remain largely unelucidated. We have studied the properties of renal H+,K+-ATPases both in vitro and in situ. Our analysis of ion fluxes driven by a nongastric H+,K+-ATPase isoform suggests that it exchanges Na (rather than H) for K under normal circumstances. Thus, the individual H+,K+-ATPase isoforms may make diverse contributions to renal cation transport. We find that the activities of renal H+,K+-ATPases in situ are regulated by endocytosis, which is mediated by an endocytosis signal in the cytoplasmic tail of the gastric H+,K+-ATPase beta-subunit. Transgenic mice expressing a version of this protein in which the signal has been disabled show constitutively active renal K resorption. The identities of the H+,K+-ATPase isoforms that are normally subject to endocytic regulation and the nature of the participating epithelial cell machinery have yet to be established.
Grishin
A V
AV
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Reinhard
J
J
Dunbar
L A
LA
Courtois-Coutry
N
N
Wang
T
T
Giebisch
G
G
Caplan
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D007685:Kidney Tubules, Collecting / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013270:Stomach / Q000201:enzymology*; D019459:Urothelium / Q000378:metabolism; D014882:Water-Electrolyte Balance
D017506:H(+)-K(+)-Exchanging ATPase