Regulation of V-ATPase activity.
V-ATPases are ATP-driven proton pumps present in both intracellular and cell surface membranes of eukaryotes that function in many normal and disease processes. V-ATPases are large, multi-subunit complexes composed of a peripheral domain (V1) that hydrolyzes ATP and a membrane integral domain (V0) that translocates protons. Because of the diversity of their functions, V-ATPase activity is controlled by a number of mechanisms. Regulated assembly of the V1and V0domains rapidly modulates V-ATPase activity in response to a variety of cues, including nutrient availability, growth factor stimulation and cellular differentiation. Considerable information has recently emerged concerning the cellular signaling pathways controlling regulated assembly. Acid secretion by epithelial cells in the kidney and epididymus is controlled by regulated trafficking of V-ATPases to the cell surface. Isoforms of subunit a of the V0domain both control trafficking of V-ATPases to distinct cellular membranes and confer properties to the resultant complexes that help account for differences in pH between cellular compartments. Finally, differential expression of genes encoding V-ATPases subunits occurs in a number of contexts, including cancer.
Program in Biochemistry, Sackler School of Graduate Biomedical Sciences, Tufts University.
Christina
C
McGuire
Program in Cell and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University.
Laura
L
Stransky
Program in Cell and Molecular Physiology, Sackler School of Graduate Biomedical Sciences, Tufts University.
Kristina
K
Cotter
Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, Michael.Forgac@tufts.edu.
Michael
M
Forgac
D000818:Animals; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000378:metabolism; D008322:Mammals; D008958:Models, Molecular; D055503:Protein Multimerization; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D019476:Insect Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D025262:Vacuolar Proton-Translocating ATPases