Comparison of the coated-vesicle and synaptic-vesicle vacuolar (H+)-ATPases.

The V-ATPases are a novel class of ATP-dependent proton pumps responsible for acidification of intracellular compartments in eukaryotic cells. They play an important role in receptor-mediated endocytosis, intracellular membrane traffic, macromolecular processing and degradation and coupled transport, as well as functioning in the plasma membrane of certain specialized cell types. The V-ATPases are multisubunit complexes that are organized into a peripheral V1 complex responsible for ATP hydrolysis and an integral V0 domain responsible for proton translocation. Regulation of vacuolar acidification is critical to its role in membrane traffic and other cellular processes. We are currently investigating several mechanisms of regulation of vacuolar acidification, including disulfide bond formation between cysteine residues located at the catalytic site, control of assembly of the peripheral and integral domains, and differential targeting of V-ATPases to different intracellular destinations using their interaction with organelle-specific adaptin complexes.