Phosphorylation and feedback regulation of metabotropic glutamate receptor 1 by calcium/calmodulin-dependent protein kinase II.
J Neurosci
; 33(8): 3402-12, 2013 Feb 20.
Article
em En
| MEDLINE
| ID: mdl-23426668
ABSTRACT
The metabotropic glutamate receptor 1 (mGluR1) is a Gα(q)-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, Ca²âº/calmodulin-dependent protein kinase IIα (CaMKIIα), directly binds to the intracellular C terminus (CT) of mGluR1a. This binding is augmented by Ca²âº 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 Ca²âº-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 Ca²âº-dependent protein-protein interaction between a synaptic kinase and mGluR1, which constitutes a feedback loop facilitating desensitization of mGluR1a.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores de Glutamato Metabotrópico
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Retroalimentação Fisiológica
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Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
Limite:
Animals
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Estados Unidos