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PKC‐dependent autoregulation of membrane kainate receptors
Author(s) -
Rivera Rocío,
Rozas José Luis,
Lerma Juan
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601865
Subject(s) - biology , kainate receptor , autoregulation , receptor , microbiology and biotechnology , biophysics , biochemistry , endocrinology , nmda receptor , ampa receptor , blood pressure
Agonists of kainate receptors (KARs) cause both the opening of the associated ion channels and the activation of signalling pathways driven by G‐proteins and PKC. Here we report the existence of an unknown mechanism of KAR autoregulation, involving the interplay of this two signalling mechanisms. Repetitive activation of native KARs evoked the rundown of the ionotropic responses in a manner that was dependent on the activation of PKC. Experiments on recombinant GluR5 expressed in neuroblastoma cells indicated that KARs trigger the activation of PKC and induce the internalization of membrane receptors. This phenomenon depends on the PKC‐mediated phosphorylation of serines 879 and 885 of the GluR5‐2b subunits, since mutation of these two residues abolished internalization. These results reveal that the non‐canonical signalling of KARs is associated with a sensitive mechanism that detects afferent activity. Such a mechanism represents an active way to limit overactivation of the KAR system, by regulating the number of KARs in the cell membrane.