Endostatin is a trans-synaptic signal for homeostatic synaptic plasticity

Neuron. 2014 Aug 6;83(3):616-29. doi: 10.1016/j.neuron.2014.07.003. Epub 2014 Jul 24.


At synapses in organisms ranging from fly to human, a decrease in postsynaptic neurotransmitter receptor function elicits a homeostatic increase in presynaptic release that restores baseline synaptic efficacy. This process, termed presynaptic homeostasis, requires a retrograde, trans-synaptic signal of unknown identity. In a forward genetic screen for homeostatic plasticity genes, we identified multiplexin. Multiplexin is the Drosophila homolog of Collagen XV/XVIII, a matrix protein that can be proteolytically cleaved to release Endostatin, an antiangiogenesis signaling factor. Here we demonstrate that Multiplexin is required for normal calcium channel abundance, presynaptic calcium influx, and neurotransmitter release. Remarkably, Endostatin has a specific activity, independent of baseline synapse development, that is required for the homeostatic modulation of presynaptic calcium influx and neurotransmitter release. Our data support a model in which proteolytic release of Endostatin signals trans-synaptically, acting in concert with the presynaptic CaV2.1 calcium channel, to promote presynaptic homeostasis.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Chondroitin Sulfate Proteoglycans / metabolism*
  • Collagen / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Endostatins / metabolism*
  • Homeostasis / physiology*
  • Humans
  • Neuronal Plasticity / physiology*
  • Neurotransmitter Agents / metabolism*
  • Signal Transduction / physiology
  • Synapses / metabolism


  • Calcium Channels
  • Chondroitin Sulfate Proteoglycans
  • Drosophila Proteins
  • Endostatins
  • Mp protein, Drosophila
  • Neurotransmitter Agents
  • Collagen
  • Calcium