Genetic and cell biological aspects of the yeast vacuolar H+-ATPase

Abstract

The yeast vacuolar proton-translocating ATPase is a member of the third class of H(+)-pumping ATPase. A family of this type of H(+)-ATPase is now known to be ubiquitously distributed in eukaryotic vacuo-lysosomal organelles and archaebacteria. Nine VMA genes that are indispensable for expression of the enzyme activity have been cloned and characterized in the yeast Saccharomyces cerevisiae. This review summarizes currently available information on the VMA genes and cell biological functions of the VMA gene products.

Subunit Interactions in the Clathrin-coated Vesicle Vacuolar (H+)-ATPase Complex

“…The vacuolar (H ϩ )-ATPases (or V-ATPases) 1 are a family of ATP-dependent proton pumps that carry out proton transport across both intracellular membranes and, in some cases, the plasma membrane (1)(2)(3)(4)(5)(6). Acidification of intracellular compartments is important for such processes as protein degradation, intracellular protein targeting, and receptor-mediated endocytosis (1-6), while V-ATPases in the plasma membrane function in renal acidification, bone resorption, and tumor metastasis (7)(8)(9).…”

“…The V-ATPase is a heteroligomeric complex of molecular mass approximately 800 kDa composed of at least 13 different subunits arranged into two separate domains (1)(2)(3)(4)(5)(6). The peripheral V 1 domain has a molecular mass of about 570 kDa and contains eight different subunits of molecular mass 70 (A), 60 (B), 57 (H), 40 (C), 34 (D), 33 (E), 14 (F), and 16 (G) kDa.…”

“…The integral V 0 domain has a molecular mass of 260 kDa and contains five different subunits of molecular mass 100 (a), 38 (d), 19 (cЉ), and 17 (c, cЈ) kDa. Functional studies indicate that the V 1 domain is responsible for ATP hydrolysis while the V 0 domain carries out proton transport (1)(2)(3)(4)(5)(6). We have previously demonstrated that each V-ATPase complex contains three copies each of the A and B subunits, six copies of the 17-kDa subunits (c, cЈ), and single copies of the C, D, E, a, d, and cЉ subunits (10).…”

Molecular Cloning and Expression of Three Isoforms of the 100-kDa a Subunit of the Mouse Vacuolar Proton-translocating ATPase

“…V-ATPases are present in a variety of intracellular compartments, including clathrin-coated vesicles, endosomes, lysosomes, Golgi-derived vesicles, chromaffin granules, synaptic vesicles, and the central vacuoles of yeast, Neurospora, and plants (1)(2)(3)(4)(5)(6)(7)(8)(9). Vacuolar acidification is essential for such processes as receptor-mediated endocytosis, intracellular targeting, protein processing and degradation, and coupled transport.…”

“…The V-ATPases of animals, plants, and fungi are structurally very similar and are composed of two functional domains (1)(2)(3)(4)(5)(6)(7)(8)(9). The V 1 domain is a peripheral complex (molecular mass, 600 -650 kDa) composed of eight different subunits ranging in molecular mass from 70 to 14 kDa (subunits A-H) that is responsible for ATP hydrolysis.…”