Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5

Robert W. Gereau IV, Stephen F. Heinemann

Research output: Contribution to journalArticle

163 Scopus citations

Abstract

Metabotropic glutamate receptors (mGluRs) coupled to phosphoinesitide hydrolysis desensitize in response to prolonged or repeated agonist exposure, and evidence suggests that this involves activation of protein kinase C (PKC). The present studies were undertaken to determine if cloned mGluR5 undergoes similar PKC-mediated desensitization and to investigate the molecular mechanism underlying PKC-induced desensitization. In Xenopus oocytes, both mGluR5a and mGluR5b showed pronounced desensitization in response to a brief activation by glutamate. Pharmacological studies clearly suggest that this desensitization requires PKC-mediated phosphorylation. Analysis of PKC consensus phosphorylation site mutants suggests that PKC phosphorylates mGluR5 at multiple sites to induce a relatively rapid form of desensitization. Because mGluRs play important roles in syneptic plasticity and in excitotoxicity, this desensitization may be involved in the dynamic regulation of these processes.

Original languageEnglish
Pages (from-to)143-151
Number of pages9
JournalNeuron
Volume20
Issue number1
DOIs
StatePublished - Jan 1998
Externally publishedYes

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