Format

Send to

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

Endostatin is a trans-synaptic signal for homeostatic synaptic plasticity.

Author information

1
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: graeme.davis@ucsf.edu.

Abstract

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.

Comment in

PMID:
25066085
PMCID:
PMC4133507
DOI:
10.1016/j.neuron.2014.07.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center