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

Neuron. 1998 Jan;20(1):143-51. doi: 10.1016/s0896-6273(00)80442-0.


Metabotropic glutamate receptors (mGluRs) coupled to phosphoinositide 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 synaptic plasticity and in excitotoxicity, this desensitization may be involved in the dynamic regulation of these processes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Female
  • Oocytes / metabolism
  • Phosphorylation
  • Point Mutation
  • Protein Kinase C / metabolism*
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate / genetics
  • Receptors, Metabotropic Glutamate / physiology*
  • Time Factors
  • Xenopus


  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Protein Kinase C