Regulation of postsynaptic retrograde signaling by presynaptic exosome release

Neuron. 2013 Mar 20;77(6):1039-46. doi: 10.1016/j.neuron.2013.01.013.


Retrograde signals from postsynaptic targets are critical during development and plasticity of synaptic connections. These signals serve to adjust the activity of presynaptic cells according to postsynaptic cell outputs and to maintain synaptic function within a dynamic range. Despite their importance, the mechanisms that trigger the release of retrograde signals and the role of presynaptic cells in this signaling event are unknown. Here we show that a retrograde signal mediated by Synaptotagmin 4 (Syt4) is transmitted to the postsynaptic cell through anterograde delivery of Syt4 via exosomes. Thus, by transferring an essential component of retrograde signaling through exosomes, presynaptic cells enable retrograde signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Exosomes / chemistry
  • Exosomes / metabolism*
  • Neuromuscular Junction / chemistry
  • Neuromuscular Junction / metabolism
  • Presynaptic Terminals / chemistry
  • Presynaptic Terminals / metabolism*
  • Signal Transduction / physiology*
  • Synapses / chemistry
  • Synapses / metabolism
  • Synaptic Potentials / physiology*
  • Synaptotagmins / metabolism*


  • Drosophila Proteins
  • Synaptotagmins