The role of Rab3A in neurotransmitter release

Nature. 1994 Jun 9;369(6480):493-7. doi: 10.1038/369493a0.

Abstract

The small GTP-binding protein Rab3A is a Rab family member that is abundant in brain synaptic vesicles. Here we show that mice in which the rab3A gene has been mutated by homologous recombination do not express Rab3A but are viable and fertile. Electrophysiological recordings in hippocampal CA1 pyramidal cells indicate that most of their synaptic parameters are also normal, although synaptic depression after short trains of repetitive stimuli (15-30 stimuli at 14 Hz) is significantly increased. Levels of the Rab3A-binding protein rabphilin are decreased by 70%, but expression of more than 20 other synaptic proteins is unchanged. No compensatory changes were detected in other GTP-binding proteins or in proteins that interact with Rab3. Rab3A thus appears not to be essential for synaptic vesicle exocytosis but to play a role in the recruitment of synaptic vesicles for exocytosis during repetitive stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Electrophysiology
  • Exocytosis / physiology
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism
  • GTP-Binding Proteins / physiology*
  • In Vitro Techniques
  • Mice
  • Mutation
  • Nerve Tissue Proteins / metabolism
  • Neurotransmitter Agents / metabolism*
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology
  • Synaptic Transmission / physiology*
  • Vesicular Transport Proteins
  • rab GTP-Binding Proteins*
  • rab3 GTP-Binding Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Nerve Tissue Proteins
  • Neurotransmitter Agents
  • Vesicular Transport Proteins
  • rabphilin-3A
  • GTP-Binding Proteins
  • rab GTP-Binding Proteins
  • rab3 GTP-Binding Proteins