The Caenorhabditis elegans unc-32 gene encodes alternative forms of a vacuolar ATPase a subunit

Eukaryotes possess multiple isoforms of the a subunit of the V-0 complex of vacuolar-type Ht-ATPases (V-ATPases). Mutations in the V-ATPase a3 isoform have recently been shown to result in osteopetrosis, a fatal disease in hu mans, but no function has yet been ascribed to other isoforms. In Caenorhab ditis elegans, the unc-32 mutant was originally isolated on the basis of it s movement defect. We have isolated four new mutant alleles, the strongest of which is embryonic lethal. We show here that unc-32 corresponds to one o f the four genes encoding a V-ATPase a subunit in the nematode, and we pres ent their expression patterns and a molecular analysis of the gene family, unc-32 gives rise via alternative splicing to at least six transcripts. In the uncoordinated alleles, the transcript unc-32 B is affected, suggesting that it encodes an isoform that is targeted to synaptic vesicles of choline rgic neurons, where it would control neurotransmitter uptake or release. Ot her isoforms expressed widely during embryogenesis are mutated in the letha l alleles and would be involved in other acidic organelles. Our results ind icate that V-ATPase a subunit genes are highly regulated and have tissue-sp ecific function.