A role for V-ATPase subunits in synaptic vesicle fusion?

J Neurochem. 2011 May;117(4):603-12. doi: 10.1111/j.1471-4159.2011.07234.x. Epub 2011 Mar 28.

Abstract

SNARE (soluble N-ethylmaleimide sensitive factor attachment protein receptors)-mediated exocytotic release of neurotransmitters is a key process in neuronal communication, controlled by a number of molecular interactions. A synaptic vesicle v-SNARE protein (VAMP2 or synaptobrevin), in association with two plasma membrane t-SNAREs (syntaxin 1 and SNAP25), assemble to form a protein complex that is largely accepted as the minimal membrane fusion machine. Acidification of the synaptic vesicle lumen by the large multi-subunit vacuolar proton pump (V-ATPase) is required for loading with neurotransmitters. Recent data demonstrate a direct interaction between the c-subunit of the V-ATPase and VAMP2 that appears to play a role at a late step in transmitter release. In this review, we examine evidence suggesting that the V0 membrane sector of the V-ATPase not only participates in proton pumping, but plays a second distinct role in neurosecretion, downstream of filling and close to vesicle fusion.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Membrane Fusion / physiology
  • Neurotransmitter Agents / metabolism
  • Proton Pumps / genetics
  • Proton Pumps / metabolism
  • SNARE Proteins / metabolism
  • Synaptic Membranes / enzymology
  • Synaptic Membranes / metabolism
  • Synaptic Vesicles / enzymology*
  • Synaptic Vesicles / physiology*
  • Synaptic Vesicles / ultrastructure
  • Synaptosomal-Associated Protein 25 / metabolism
  • Syntaxin 1 / metabolism
  • Vacuolar Proton-Translocating ATPases / metabolism*
  • Vesicle-Associated Membrane Protein 2 / metabolism

Substances

  • Neurotransmitter Agents
  • Proton Pumps
  • SNARE Proteins
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1
  • Vesicle-Associated Membrane Protein 2
  • Vacuolar Proton-Translocating ATPases