Neurexin mediates the assembly of presynaptic terminals

Camin Dean

Francisco Scholl

Jenny Choih

Shannon DeMaria

James Berger

Ehud Isacoff

Peter Scheiffele

^{Department of Molecular and Cell Biology, University of California, Berkeley, 271 LSA, California 94720, USA.}

^{Columbia University, Department of Physiology & Cellular Biophysics, College of Physicians & Surgeons, Center for Neurobiology and Behavior, New York, New York 10032, USA.}

^{These authors contributed equally to this work.}

* Correspondence should be addressed to P.S. (ude.aibmuloc@8102sp).

Abstract

Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.

Abstract

Footnotes

Note: Supplementary information is available on the Nature Neuroscience website.

COMPETING INTERESTS STATEMENT The authors declare that they have no competing financial interests.

Footnotes

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