Neurexin-1β Binding to Neuroligin-1 Triggers the Preferential Recruitment of PSD-95 versus Gephyrin through Tyrosine Phosphorylation of Neuroligin-1

Grégory Giannone, Magali Mondin, Dolors Grillo-Bosch, Béatrice Tessier, Edouard Saint-Michel, Katalin Czöndör, Matthieu Sainlos, Daniel Choquet, Olivier Thoumine
Cell Reports. 2013-06-01; 3(6): 1996-2007
DOI: 10.1016/j.celrep.2013.05.013

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1. Cell Rep. 2013 Jun 27;3(6):1996-2007. doi: 10.1016/j.celrep.2013.05.013. Epub
2013 Jun 13.

Neurexin-1β binding to neuroligin-1 triggers the preferential recruitment of
PSD-95 versus gephyrin through tyrosine phosphorylation of neuroligin-1.

Giannone G(1), Mondin M, Grillo-Bosch D, Tessier B, Saint-Michel E, Czöndör K,
Sainlos M, Choquet D, Thoumine O.

Author information:
(1)University Bordeaux, Interdisciplinary Institute for Neuroscience, UMR 5297,
F-33000 Bordeaux, France.

Adhesion between neurexin-1β (Nrx1β) and neuroligin-1 (Nlg1) induces early
recruitment of the postsynaptic density protein 95 (PSD-95) scaffold; however,
the associated signaling mechanisms are unknown. To dissociate the effects of
ligand binding and receptor multimerization, we compared conditions in which Nlg1
in neurons was bound to Nrx1β or nonactivating HA antibodies. Time-lapse imaging,
fluorescence recovery after photobleaching, and single-particle tracking
demonstrated that in addition to aggregating Nlg1, Nrx1β binding stimulates the
interaction between Nlg1 and PSD-95. Phosphotyrosine immunoblots and pull-down of
gephyrin by Nlg1 peptides in vitro showed that Nlg1 can be phosphorylated at a
unique tyrosine (Y782), preventing gephyrin binding. Expression of Nlg1 point
mutants in neurons indicated that Y782 phosphorylation controls the preferential
binding of Nlg1 to PSD-95 versus gephyrin, and accordingly the formation of
inhibitory and excitatory synapses. We propose that ligand-induced changes in the
Nlg1 phosphotyrosine level control the balance between excitatory and inhibitory
scaffold assembly during synapse formation and stabilization.

Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.celrep.2013.05.013
PMID: 23770246 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus