Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells.
Nat Comms. 2016-09-27; 7: 12738
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1. Nat Commun. 2016 Sep 27;7:12738. doi: 10.1038/ncomms12738.
Molecular determinants for the strictly compartmentalized expression of kainate
receptors in CA3 pyramidal cells.
Fièvre S(1), Carta M(1), Chamma I(1), Labrousse V(1), Thoumine O(1), Mulle C(1).
(1)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of
Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Distinct subtypes of ionotropic glutamate receptors can segregate to specific
synaptic inputs in a given neuron. Using functional mapping by focal glutamate
uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs)
are strictly confined to the postsynaptic elements of mossy fibre (mf) synapses
and excluded from other glutamatergic inputs and from extrasynaptic compartments.
By molecular replacement in organotypic slices from GluK2 knockout mice, we show
that the faithful rescue of KAR segregation at mf-CA3 synapses critically depends
on the amount of GluK2a cDNA transfected and on a sequence in the GluK2a
C-terminal domain responsible for interaction with N-cadherin. Targeted deletion
of N-cadherin in CA3 PCs greatly reduces KAR content in thorny excrescences and
KAR-EPSCs at mf-CA3 synapses. Hence, multiple mechanisms combine to confine KARs
at mf-CA3 synapses, including a stringent control of the amount of GluK2 subunit
in CA3 PCs and the recruitment/stabilization of KARs by N-cadherins.