Alternative splicing controls neuronal expression of v-ATPase subunit a1 and sorting to nerve terminals

J Biol Chem. 2006 Jun 23;281(25):17164-17172. doi: 10.1074/jbc.M600927200. Epub 2006 Apr 18.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Exons
  • Gene Expression Regulation
  • Hippocampus / cytology
  • Hippocampus / embryology
  • Microscopy, Fluorescence
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Protein Isoforms
  • Protons
  • Rats
  • Tissue Distribution
  • Transfection
  • Vacuolar Proton-Translocating ATPases / biosynthesis*
  • Vacuolar Proton-Translocating ATPases / genetics


  • Protein Isoforms
  • Protons
  • v-ATPase subunit a1, rat
  • Vacuolar Proton-Translocating ATPases
  • vacuolar ATPase V0 subunit A1, rat