Format

Send to

Choose Destination
Neuron. 2012 Oct 18;76(2):396-409. doi: 10.1016/j.neuron.2012.07.006. Epub 2012 Oct 17.

Transsynaptic signaling by activity-dependent cleavage of neuroligin-1.

Author information

1
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.

Erratum in

  • Neuron. 2012 Nov 8;76(3):667.

Abstract

Adhesive contact between pre- and postsynaptic neurons initiates synapse formation during brain development and provides a natural means of transsynaptic signaling. Numerous adhesion molecules and their role during synapse development have been described in detail. However, once established, the mechanisms of adhesive disassembly and its function in regulating synaptic transmission have been unclear. Here, we report that synaptic activity induces acute proteolytic cleavage of neuroligin-1 (NLG1), a postsynaptic adhesion molecule at glutamatergic synapses. NLG1 cleavage is triggered by NMDA receptor activation, requires Ca2+ /calmodulin-dependent protein kinase, and is mediated by proteolytic activity of matrix metalloprotease 9 (MMP9). Cleavage of NLG1 occurs at single activated spines, is regulated by neural activity in vivo, and causes rapid destabilization of its presynaptic partner neurexin-1β (NRX1β). In turn, NLG1 cleavage depresses synaptic transmission by abruptly reducing presynaptic release probability. Thus, local proteolytic control of synaptic adhesion tunes synaptic transmission during brain development and plasticity.

Comment in

PMID:
23083741
PMCID:
PMC3783515
DOI:
10.1016/j.neuron.2012.07.006
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

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