Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds

J Neurosci. 2011 Sep 21;31(38):13500-15. doi: 10.1523/JNEUROSCI.6439-10.2011.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal / biosynthesis*
  • Cell Adhesion Molecules, Neuronal / genetics
  • Disks Large Homolog 4 Protein
  • Female
  • Guanylate Kinases / antagonists & inhibitors
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism*
  • Hippocampus / metabolism
  • Hippocampus / physiology*
  • Male
  • Membrane Potentials / genetics
  • Membrane Potentials / physiology
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Mutation
  • Neural Cell Adhesion Molecules / metabolism*
  • Patch-Clamp Techniques / methods
  • Primary Cell Culture
  • Rats
  • Receptors, AMPA / metabolism*
  • Receptors, AMPA / physiology
  • Synaptic Transmission / genetics
  • Synaptic Transmission / physiology*
  • Transfection / methods


  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Membrane Proteins
  • Neural Cell Adhesion Molecules
  • Nrxn1 protein, mouse
  • Receptors, AMPA
  • neuroligin 1
  • Guanylate Kinases