Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 27669960.
- Also identified by DOI 10.1038/ncomms12738 and PMC identifier 5052629.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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.