Alternative splicing controls neuronal expression of v-ATPase subunit a1 and sorting to nerve terminals.
Vacuolar proton ATPase accumulates protons inside various intracellular organelles such as synaptic vesicles; its membrane domain V0 could also be involved in membrane fusion. These different functions could require vacuolar proton ATPases possessing different V0 subunit a isoforms. In vertebrates, four genes encode isoforms a1-a4, and a1 variants are also generated by alternative splicing. We identified a novel a1 splice variant a1-IV and showed that the two a1 variants containing exon C are specifically expressed in neurons. Single neurons coexpress a2, a1-I, and a1-IV, and these subunit a isoforms are targeted to different membrane compartments. Recombinant a2 was accumulated in the trans-Golgi network, and a1-I was concentrated in axonal varicosities, whereas a1-IV was sorted to both distal dendrites and axons. Our results indicate that alternative splicing of exon N controls differential sorting of a1 variants to nerve terminals or distal dendrites, whereas exon C regulates their neuronal expression.
Poëa-Guyon
Sandrine
S
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR9040, 91198 Gif sur Yvette, France.
Amar
Muriel
M
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR9040, 91198 Gif sur Yvette, France.
Fossier
Philippe
P
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR9040, 91198 Gif sur Yvette, France.
Morel
Nicolas
N
Laboratoire de Neurobiologie Cellulaire et Moléculaire, CNRS UPR9040, 91198 Gif sur Yvette, France. Electronic address: nicolas.morel@nbcm.cnrs-gif.fr.
D017398:Alternative Splicing; D000818:Animals; D005091:Exons; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms; D011522:Protons; D051381:Rats; D014018:Tissue Distribution; D014162:Transfection; D025262:Vacuolar Proton-Translocating ATPases / Q000096:biosynthesis* / Q000235:genetics
D020033:Protein Isoforms; D011522:Protons; C512320:v-ATPase subunit a1, rat; D025262:Vacuolar Proton-Translocating ATPases; C569187:vacuolar ATPase V0 subunit A1, rat