Structure, function and regulation of the vacuolar (H+)-ATPases.
The vacuolar (H+)-ATPases (or V-ATPases) function to acidify intracellular compartments in eukaryotic cells, playing an important role in such processes as receptor-mediated endocytosis, intracellular membrane traffic, protein degradation and coupled transport. V-ATPases in the plasma membrane of specialized cells also function in renal acidification, bone resorption and cytosolic pH maintenance. The V-ATPases are composed of two domains. The V1 domain is a 570-kDa peripheral complex composed of 8 subunits (subunits A-H) of molecular weight 70-13 kDa which is responsible for ATP hydrolysis. The V0 domain is a 260-kDa integral complex composed of 5 subunits (subunits a-d) which is responsible for proton translocation. The V-ATPases are structurally related to the F-ATPases which function in ATP synthesis. Biochemical and mutational studies have begun to reveal the function of individual subunits and residues in V-ATPase activity. A central question in this field is the mechanism of regulation of vacuolar acidification in vivo. Evidence has been obtained suggesting a number of possible mechanisms of regulating V-ATPase activity, including reversible dissociation of V1 and V0 domains, disulfide bond formation at the catalytic site and differential targeting of V-ATPases. Control of anion conductance may also function to regulate vacuolar pH. Because of the diversity of functions of V-ATPases, cells most likely employ multiple mechanisms for controlling their activity.
Forgac
M
M
Department of Cellular and Molecular Physiology, Tufts University School of Medicine, Boston, MA 02111, USA. mforgac@opal.tufts.edu
D004705:Endocytosis; D005057:Eukaryotic Cells; D017136:Ion Transport; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D013329:Structure-Activity Relationship; D025262:Vacuolar Proton-Translocating ATPases; D014617:Vacuoles / Q000201:enzymology* / Q000502:physiology; D015003:Yeasts
D025262:Vacuolar Proton-Translocating ATPases; D006180:Proton-Translocating ATPases