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Regulation of metabotropic glutamate receptor 7 (mGluR7) internalization and surface expression by Ser/Thr protein phosphatase 1.

Suh, YH; Park, JY; Park, S; Jou, I; Roche, PA; Roche, KW
The Journal of biological chemistry, 288(24):17544-17551, 2013
Journal Title
The Journal of biological chemistry
The metabotropic glutamate receptor type 7 (mGluR7) is the predominant group III mGluR in the presynaptic active zone, where it serves as an autoreceptor to inhibit neurotransmitter release. Our previous studies show that PKC phosphorylation of mGluR7 on Ser-862 is a key mechanism controlling constitutive and activity-dependent surface expression of mGluR7 by regulating a competitive interaction of calmodulin and protein interacting with C kinase (PICK1). As receptor phosphorylation and dephosphorylation are tightly coordinated through the precise action of protein kinases and phosphatases, dephosphorylation by phosphatases is likely to play an active role in governing the activity-dependent or agonist-induced changes in mGluR7 receptor surface expression. In the present study, we find that the serine/threonine protein phosphatase 1 (PP1) has a crucial role in the constitutive and agonist-induced dephosphorylation of Ser-862 on mGluR7. Treatment of neurons with PP1 inhibitors leads to a robust increase in Ser-862 phosphorylation and increased surface expression of mGluR7. In addition, Ser-862 phosphorylation of both mGluR7a and mGluR7b is a target of PP1. Interestingly, agonist-induced dephosphorylation of mGluR7 is regulated by PP1, whereas NMDA-mediated activity-induced dephosphorylation is not, illustrating there are multiple signaling pathways that affect receptor phosphorylation and trafficking. Importantly, PP1γ1 regulates agonist-dependent Ser-862 dephosphorylation and surface expression of mGluR7.
MeSH terms
Aminobutyrates/pharmacologyAnimalsEndocytosisExcitatory Amino Acid Agonists/pharmacologyHEK293 CellsHippocampus/cytologyHumansN-Methylaspartate/pharmacologyNeurons/enzymologyPhosphorylationPrimary Cell CultureProtein Phosphatase 1/antagonists & inhibitors/*physiologyProtein Processing, Post-TranslationalProtein TransportRatsRats, Sprague-DawleyReceptors, Metabotropic Glutamate/agonists/*metabolism
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Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
서, 영호박, 상욱주, 일로
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