Phosphorylation and feedback regulation of metabotropic glutamate receptor 1 by calcium/calmodulin-dependent protein kinase II

Dao Zhong Jin, Ming Lei Guo, Bing Xue, Eugene E. Fibuch, Eun Sang Choe, Li Min Mao, John Q. Wang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The metabotropic glutamate receptor 1 (mGluR1) is a Gαq-protein-coupled receptor and is distributed in broad regions of the mammalian brain. As a key element in excitatory synaptic transmission, the receptor regulates a wide range of cellular and synaptic activities. In addition to regulating its targets, the receptor itself is believed to be actively regulated by intracellular signals, although underlying mechanisms are essentially unknown. Here we found that a synapse-enriched protein kinase, Ca 2+ /calmodulin-dependent protein kinase IIα (CaMKIIα), directly binds to the intracellular C terminus (CT) of mGluR1a. This binding is augmented by Ca 2+ in vitro. The direct interaction promotes CaMKIIα to phosphorylate mGluR1a at a specific threonine site (T871). In rat striatal neurons, the mGluR1 agonist triggers the receptor-associated phosphoinositide signaling pathway to induce Ca 2+ -dependent recruitment of CaMKIIα to mGluR1a-CT. This enables the kinase to inhibit the response of the receptor to subsequent agonist exposure. Our data identify an agonist-induced and Ca 2+ -dependent protein-protein interaction between a synaptic kinase and mGluR1, which constitutes a feedback loop facilitating desensitization of mGluR1a.

Original languageEnglish (US)
Pages (from-to)3402-3412
Number of pages11
JournalJournal of Neuroscience
Volume33
Issue number8
DOIs
StatePublished - Feb 20 2013

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Phosphorylation
Phosphotransferases
Gq-G11 GTP-Binding Protein alpha Subunits
Corpus Striatum
Neurotransmitter Receptor
Threonine
metabotropic glutamate receptor type 1
Synaptic Transmission
Synapses
Protein Kinases
Proteins
Neurons
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Phosphorylation and feedback regulation of metabotropic glutamate receptor 1 by calcium/calmodulin-dependent protein kinase II. / Jin, Dao Zhong; Guo, Ming Lei; Xue, Bing; Fibuch, Eugene E.; Choe, Eun Sang; Mao, Li Min; Wang, John Q.

In: Journal of Neuroscience, Vol. 33, No. 8, 20.02.2013, p. 3402-3412.

Research output: Contribution to journalArticle

Jin, Dao Zhong ; Guo, Ming Lei ; Xue, Bing ; Fibuch, Eugene E. ; Choe, Eun Sang ; Mao, Li Min ; Wang, John Q. / Phosphorylation and feedback regulation of metabotropic glutamate receptor 1 by calcium/calmodulin-dependent protein kinase II. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 8. pp. 3402-3412.
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