Vacuolar (H+)-ATPases in Caenorhabditis elegans: What can we learn about giant H+ pumps from tiny worms?

Vacuolar (H+)-ATPases, also called V-ATPases, are ATP-driven proton pumps that are highly phylogenetically conserved. Early biochemical and cell biological studies have revealed many details of the molecular mechanism of proton pumping and of the structure of the multi-subunit membrane complex, including the stoichiometry of subunit composition. In addition, yeast and mouse genetics have broadened our understanding of the physiological consequences of defective vacuolar acidification and its related disease etiologies. Recently, phenotypic investigation of V-ATPase mutants in Caenorhabditis elegans has revealed unexpected new roles of V-ATPases in both cellular function and early development. In this review, we discuss the functions of the V-ATPases discovered in C. elegans.

Research highlights
► In Caenorhabditis elegans, V-ATPase is required for development and osmoregulation.
► Vo domain of V-ATPase is critical for secretion and cell–cell fusion in worms.
► V-ATPase is spatio-temporally regulated in the secretory pathway during development.
► V-ATPase is required in necrotic cell death and intestinal rhythmic acidification.
► C. elegans can be a useful model for research and drug targeting of V-ATPase.