title: Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds.
abstract: The mechanisms governing the recruitment of functional glutamate receptors at nascent excitatory postsynapses following initial axon-dendrite contact remain unclear. We examined here the ability of neurexin/neuroligin adhesions to mobilize AMPA-type glutamate receptors (AMPARs) at postsynapses through a diffusion/trap process involving the scaffold molecule PSD-95. Using single nanoparticle tracking in primary rat and mouse hippocampal neurons overexpressing or lacking neuroligin-1 (Nlg1), a striking inverse correlation was found between AMPAR diffusion and Nlg1 expression level. The use of Nlg1 mutants and inhibitory RNAs against PSD-95 demonstrated that this effect depended on intact Nlg1/PSD-95 interactions. Furthermore, functional AMPARs were recruited within 1 h at nascent Nlg1/PSD-95 clusters assembled by neurexin-1β multimers, a process requiring AMPAR membrane diffusion. Triggering novel neurexin/neuroligin adhesions also caused a depletion of PSD-95 from native synapses and a drop in AMPAR miniature EPSCs, indicating a competitive mechanism. Finally, both AMPAR level at synapses and AMPAR-dependent synaptic transmission were diminished in hippocampal slices from newborn Nlg1 knock-out mice, confirming an important role of Nlg1 in driving AMPARs to nascent synapses. Together, these data reveal a mechanism by which membrane-diffusing AMPARs can be rapidly trapped at PSD-95 scaffolds assembled at nascent neurexin/neuroligin adhesions, in competition with existing synapses.
authors.affiliation: Interdisciplinary Institute of Neurosciences, CNRS, UMR 5297, Université de Bordeaux, 33077 Bordeaux, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Mondin
authors.forename: Virginie
authors.initials: V
authors.lastname: Labrousse
authors.forename: Eric
authors.initials: E
authors.lastname: Hosy
authors.forename: Martin
authors.initials: M
authors.lastname: Heine
authors.forename: Béatrice
authors.initials: B
authors.lastname: Tessier
authors.forename: Florian
authors.initials: F
authors.lastname: Levet
authors.forename: Christel
authors.initials: C
authors.lastname: Poujol
authors.forename: Christophe
authors.initials: C
authors.lastname: Blanchet
authors.forename: Daniel
authors.initials: D
authors.lastname: Choquet
authors.forename: Olivier
authors.initials: O
authors.lastname: Thoumine
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D051528:Guanylate Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000235:genetics / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D061251:Primary Cell Culture; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism* / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; C527193:Nrxn1 protein, mouse; D018091:Receptors, AMPA; C093438:neuroligin 1; D051528:Guanylate Kinases