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

• DOI: 10.1016/j.celrep.2013.05.013
• Publication Date: 2013-06-13T15:32:27Z
• Authors: Grégory Giannone; Magali Mondin; Dolors Grillo-Bosch; Béatrice Tessier; Edouard Saint-Michel; Katalin Czöndör; Matthieu Sainlos; Daniel Choquet; Olivier Thoumine
• Keywords: Gephyrin; Neuroligin; Neurexin; Postsynaptic density

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