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 H(+)-ATPases (V-ATPases). Mutations in the V-ATPase a3 isoform have recently been shown to result in osteopetrosis, a fatal disease in humans, but no function has yet been ascribed to other isoforms. In Caenorhabditis elegans, the unc-32 mutant was originally isolated on the basis of its 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 of the four genes encoding a V-ATPase a subunit in the nematode, and we present 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 cholinergic neurons, where it would control neurotransmitter uptake or release. Other isoforms expressed widely during embryogenesis are mutated in the lethal alleles and would be involved in other acidic organelles. Our results indicate that V-ATPase a subunit genes are highly regulated and have tissue-specific function.
Pujol
N
N
Laboratoire de Génétique et Physiologie du Développement, CNRS, INSERM, Université de la Méditerranée, Luminy Case 907, 13288 Marseille Cedex 9, France. pujol@ibdm.univ-mrs.fr
Bonnerot
C
C
Ewbank
J J
JJ
Kohara
Y
Y
Thierry-Mieg
D
D
D000483:Alleles; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D019143:Evolution, Molecular; D005804:Genes, Lethal; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D006180:Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D025262:Vacuolar Proton-Translocating ATPases
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D012333:RNA, Messenger; C506985:vha-11 protein, C elegans; C506986:vha-2 protein, C elegans; C506987:vha-3 protein, C elegans; D025262:Vacuolar Proton-Translocating ATPases; C506981:unc-32 protein, C elegans; D006180:Proton-Translocating ATPases