Kidney vacuolar H+ -ATPase: physiology and regulation.
The vacuolar H(+)-ATPase is a multisubunit protein consisting of a peripheral catalytic domain (V(1)) that binds and hydrolyzes adenosine triphosphate (ATP) and provides energy to pump H(+) through the transmembrane domain (V(0)) against a large gradient. This proton-translocating vacuolar H(+)-ATPase is present in both intracellular compartments and the plasma membrane of eukaryotic cells. Mutations in genes encoding kidney intercalated cell-specific V(0) a4 and V(1) B1 subunits of the vacuolar H(+)-ATPase cause the syndrome of distal tubular renal acidosis. This review focuses on the function, regulation, and the role of vacuolar H(+)-ATPases in renal physiology. The localization of vacuolar H(+)-ATPases in the kidney, and their role in intracellular pH (pHi) regulation, transepithelial proton transport, and acid-base homeostasis are discussed.
Valles
Patricia
P
Area de Fisiopatología, Departamento de Patología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza, Argentina.
Lapointe
Michael S
MS
Wysocki
Jan
J
Batlle
Daniel
D
D000141:Acidosis, Renal Tubular / Q000503:physiopathology; D000199:Actins / Q000378:metabolism; D000471:Alkalosis / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D007684:Kidney Tubules / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012084:Renin-Angiotensin System / Q000502:physiology; D050600:SNARE Proteins / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers; D022161:Transport Vesicles / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*
D000199:Actins; D002352:Carrier Proteins; D002712:Chlorides; D010750:Phosphoproteins; D050600:SNARE Proteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor; D025262:Vacuolar Proton-Translocating ATPases