VMA8 encodes the D subunit of the yeast V-ATPase V₁ domain (1, 4). Vacuolar (H )-ATPases (V-ATPases) are ATP-dependent proton pumps that acidify intracellular vacuolar compartments. Vacuolar acidification is important for many cellular processes, including endocytosis, targeting of newly synthesized lysosomal enzymes, and other molecular targeting processes. The V-ATPase consists of two separable domains. The V₁ domain has eight known subunits, is peripherally associated with the vacuolar membrane, and catalyzes ATP hydrolysis. The V₀ domain is an integral membrane structure of five subunits, and transports protons across the membrane. The structure, function, and assembly of V-ATPases are reviewed in references 3, 5, 6 and 7.

The vma8 null mutant is viable but lacks vacuolar (H )-ATPase activity, cannot grow at neutral pH or on nonfermentable carbon sources, and fails to accumulate quinacrine in the vacuole (1, 4). In the absence of Vma8p, the remaining V₁ subunits do not associate with the vacuolar membrane (1). A specific interaction between Vma8p and the V-ATPase F subunit (Vma7p) has been detected (8). Several mutations in VMA8 cause uncoupling of proton transport from ATPase activity, suggesting that the D subunit normally plays an important role in coupling these activities (2).

V-ATPases have been identified in numerous eukaryotes (3, 7); a bovine cDNA encoding a homolog of the V-ATPase D subunit has been cloned (4).

Last updated: 2000-05-15