title: Regulation of metabotropic glutamate receptor 7 (mGluR7) internalization and surface expression by Ser/Thr protein phosphatase 1.
abstract: 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.
authors.affiliation: Department of Pharmacology and Chronic Inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-721, South Korea. suhy@ajou.ac.kr
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Suh
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Sangwook
authors.initials: S
authors.lastname: Park
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.forename: Paul A
authors.initials: PA
authors.lastname: Roche
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Roche
mesh_terms: D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D004705:Endocytosis; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000201:enzymology; D010766:Phosphorylation; D061251:Primary Cell Culture; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*
chemical_list: D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7; D016202:N-Methylaspartate; D054645:Protein Phosphatase 1; C012729:2-amino-4-phosphonobutyric acid
keywords: G Protein Coupled Receptors (GPCR); Glutamate Receptor Metabotropic; Protein Phosphorylation; Receptor Endocytosis; Serine Threonine Protein Phosphatase; Synapses