Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds.
Journal of Neuroscience. 2011-09-21; 31(38): 13500-13515
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1. J Neurosci. 2011 Sep 21;31(38):13500-15. doi: 10.1523/JNEUROSCI.6439-10.2011.
Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through
Mondin M(1), Labrousse V, Hosy E, Heine M, Tessier B, Levet F, Poujol C, Blanchet
C, Choquet D, Thoumine O.
(1)Interdisciplinary Institute of Neurosciences, CNRS, UMR 5297, Université de
Bordeaux, 33077 Bordeaux, France.
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.
PMID: 21940442 [Indexed for MEDLINE]