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INVITED REVIEW

New insights into the regulation of V-ATPase-dependent proton secretion

Program in Membrane Biology, Nephrology Division, Massachusetts General Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts

Submitted 29 August 2006 ; accepted in final form 5 October 2006

The vacuolar H⁺-ATPase (V-ATPase) is a key player in several aspects of cellular function, including acidification of intracellular organelles and regulation of extracellular pH. In specialized cells of the kidney, male reproductive tract and osteoclasts, proton secretion via the V-ATPase represents a major process for the regulation of systemic acid/base status, sperm maturation and bone resorption, respectively. These processes are regulated via modulation of the plasma membrane expression and activity of the V-ATPase. The present review describes selected aspects of V-ATPase regulation, including recycling of V-ATPase-containing vesicles to and from the plasma membrane, assembly/disassembly of the two domains (V₀ and V₁) of the holoenzyme, and the coupling ratio between ATP hydrolysis and proton pumping. Modulation of the V-ATPase-rich cell phenotype and the pathophysiology of the V-ATPase in humans and experimental animals are also discussed.

proton-pumping ATPase; epididymis; kidney; cytoskeleton; plasma membrane; vesicle trafficking

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