Interplay between VGLUT isoforms and endophilin A1 regulates neurotransmitter release and short-term plasticity

Neuron. 2011 Mar 24;69(6):1147-59. doi: 10.1016/j.neuron.2011.02.002.


Vesicular glutamate transporters (VGLUTs) are essential for filling synaptic vesicles with glutamate and mammals express three VGLUT isoforms (VGLUT1-3) with distinct spatiotemporal expression patterns. Here, we find that neurons expressing VGLUT1 have lower release probability and less short-term depression than neurons expressing VGLUT2 or VGLUT3. Investigation of the underlying mechanism identified endophilin A1 as a positive regulator of exocytosis whose expression levels are positively correlated with release efficiency and showed that the differences in release efficiency between VGLUT1- and VGLUT2-expressing neurons are due to VGLUT1's ability to bind endophilin A1 and inhibit endophilin-induced enhancement of release probability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Binding Sites / physiology
  • Cells, Cultured
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / physiology
  • Mice
  • Mice, Knockout
  • Miniature Postsynaptic Potentials / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Protein Isoforms / metabolism*
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / metabolism
  • Vesicular Glutamate Transport Proteins / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Protein Isoforms
  • Vesicular Glutamate Transport Proteins
  • endophilin A1 protein, mouse