Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5 - PubMed (original) (raw)
Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5
R W Gereau 4th et al. Neuron. 1998 Jan.
Free article
Abstract
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.
Similar articles
- Effects of ethanol and anesthetics on type 1 and 5 metabotropic glutamate receptors expressed in Xenopus laevis oocytes.
Minami K, Gereau RW 4th, Minami M, Heinemann SF, Harris RA. Minami K, et al. Mol Pharmacol. 1998 Jan;53(1):148-56. doi: 10.1124/mol.53.1.148. Mol Pharmacol. 1998. PMID: 9443943 - Mechanisms of metabotropic glutamate receptor desensitization: role in the patterning of effector enzyme activation.
Dale LB, Babwah AV, Ferguson SS. Dale LB, et al. Neurochem Int. 2002 Nov;41(5):319-26. doi: 10.1016/s0197-0186(02)00073-6. Neurochem Int. 2002. PMID: 12176073 Review. - Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5.
Lee JH, Lee J, Choi KY, Hepp R, Lee JY, Lim MK, Chatani-Hinze M, Roche PA, Kim DG, Ahn YS, Kim CH, Roche KW. Lee JH, et al. Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12575-80. doi: 10.1073/pnas.0712033105. Epub 2008 Aug 20. Proc Natl Acad Sci U S A. 2008. PMID: 18715999 Free PMC article. - Regulation of metabotropic glutamate receptor signaling, desensitization and endocytosis.
Dhami GK, Ferguson SS. Dhami GK, et al. Pharmacol Ther. 2006 Jul;111(1):260-71. doi: 10.1016/j.pharmthera.2005.01.008. Epub 2006 Mar 6. Pharmacol Ther. 2006. PMID: 16574233 Review.
Cited by
- Deficits in ventromedial prefrontal cortex group 1 metabotropic glutamate receptor function mediate resistance to extinction during protracted withdrawal from an extensive history of cocaine self-administration.
Ben-Shahar O, Sacramento AD, Miller BW, Webb SM, Wroten MG, Silva HE, Caruana AL, Gordon EJ, Ploense KL, Ditzhazy J, Kippin TE, Szumlinski KK. Ben-Shahar O, et al. J Neurosci. 2013 Jan 9;33(2):495-506a. doi: 10.1523/JNEUROSCI.3710-12.2013. J Neurosci. 2013. PMID: 23303930 Free PMC article. - Regulation of synaptic transmission by ambient extracellular glutamate.
Featherstone DE, Shippy SA. Featherstone DE, et al. Neuroscientist. 2008 Apr;14(2):171-81. doi: 10.1177/1073858407308518. Epub 2007 Oct 18. Neuroscientist. 2008. PMID: 17947494 Free PMC article. Review. - mGluR5 antagonism inhibits cocaine reinforcement and relapse by elevation of extracellular glutamate in the nucleus accumbens via a CB1 receptor mechanism.
Li X, Peng XQ, Jordan CJ, Li J, Bi GH, He Y, Yang HJ, Zhang HY, Gardner EL, Xi ZX. Li X, et al. Sci Rep. 2018 Feb 27;8(1):3686. doi: 10.1038/s41598-018-22087-1. Sci Rep. 2018. PMID: 29487381 Free PMC article. - Metabotropic glutamate receptor trafficking.
Suh YH, Chang K, Roche KW. Suh YH, et al. Mol Cell Neurosci. 2018 Sep;91:10-24. doi: 10.1016/j.mcn.2018.03.014. Epub 2018 Mar 29. Mol Cell Neurosci. 2018. PMID: 29604330 Free PMC article. Review. - Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1.
Kiritoshi T, Sun H, Ren W, Stauffer SR, Lindsley CW, Conn PJ, Neugebauer V. Kiritoshi T, et al. Neuropharmacology. 2013 Mar;66:170-8. doi: 10.1016/j.neuropharm.2012.03.024. Epub 2012 Apr 6. Neuropharmacology. 2013. PMID: 22521499 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources