TY - JOUR
T1 - Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5
AU - Gereau IV, Robert W.
AU - Heinemann, Stephen F.
N1 - Funding Information:
The authors thank Dr. Jean-Philippe Pin for supplying the original mGluR5a and 5b constructs; C. Maron, M. Hartley, and C. Whiting for technical assistance; and P. J. Conn and G. Swanson for many helpful discussions. This work was supported by grants from the National Institutes of Health (R. W. G. and S. F. H.) and a grant from the McKnight Foundation (S. F. H.).
PY - 1998/1
Y1 - 1998/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/0031932286
U2 - 10.1016/S0896-6273(00)80442-0
DO - 10.1016/S0896-6273(00)80442-0
M3 - Article
C2 - 9459450
AN - SCOPUS:0031932286
SN - 0896-6273
VL - 20
SP - 143
EP - 151
JO - Neuron
JF - Neuron
IS - 1
ER -