V-ATPase V1 Sector Is Required for Corpse Clearance and Neurotransmission in Caenorhabditis elegans

The vacuolar-type ATPase (V-ATPase) is a proton pump composed of two sectors, the cytoplasmic V-1 sector that catalyzes ATP hydrolysis and the transmembrane V-o sector responsible for proton translocation. The transmembrane V-o complex directs the complex to different membranes, but also has been proposed to have roles independent of the V-1 sector. However, the roles of the V-1 sector have not been well characterized. In the nematode Caenorhabditis elegans there are two V-1 B-subunit genes; one of them, vha-12, is on the X chromosome, whereas spe-5 is on an autosome. vha-12 is broadly expressed in adults, and homozygotes for a weak allele in vha-12 are viable but are uncoordinated due to decreased neurotransmission. Analysis of a null mutation demonstrates that vha-12 is not required for oogenesis or spermatogenesis in the adult germ line, but it is required maternally for early embryonic development. Zygotic expression begins during embryonic morphogenesis, and homozygous null mutants arrest at the twofold stage. These mutant embryos exhibit a defect in the clearance of apoptotic cell corpses in vha-12 null mutants. These observations indicate that the V-1 sector, in addition to the V-o sector, is required in exocytic and endocytic pathways.