Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells.
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.
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Sabine
S
Fièvre
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Mario
M
Carta
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Ingrid
I
Chamma
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Virginie
V
Labrousse
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Olivier
O
Thoumine
Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of Bordeaux, 146 rue Léo-Saignat, F-33076 Bordeaux, France.
Christophe
C
Mulle
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