title: Regulation of phosphorylation at Ser(1303) of GluN2B receptor in the postsynaptic density.
abstract: Neuronal N-methyl-D-aspartate subtype of ionotropic glutamate receptor (NMDAR) that plays essential roles in excitatory synaptic transmission is regulated by phosphorylation. However, the kinases and phosphatases involved in this regulation are not completely known. We show that the GluN2B subunit of NMDAR is phosphorylated at Ser(1303) by protein kinase C (PKC) and is dephosphorylated by protein phosphatase 1 (PP1), but not protein phosphatase 2A (PP2A) in isolated postsynaptic density (PSD). Although PSD is known to harbor PKC, PP1 and PP2A, their ability to regulate phosphorylation of GluN2B-Ser(1303) would depend on the accessibility of GluN2B-Ser(1303) to these proteins. Since PSD preparation is likely to maintain the organization of its component proteins as inside neurons, accessibility of kinases and phosphatases to GluN2B-Ser(1303)in vivo would be addressed by experiments using this system. Using an antibody specific for the phosphorylated state of GluN2B-Ser(1303) we demonstrate that PP1 is the major phosphatase in rat brain PSD that can dephosphorylate the GluN2B-Ser(1303) endogenous to PSD. We also show that PKC present in PSD can phosphorylate GluN2B-Ser(1303). The events reported here might be important in regulating GluN2B-Ser(1303) phosphorylation in vivo.
authors.affiliation: Molecular Neurobiology Division, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.
authors.forename: R
authors.initials: R
authors.lastname: Prabhu Ramya
authors.forename: S
authors.initials: S
authors.lastname: Suma Priya
authors.forename: M
authors.initials: M
authors.lastname: Mayadevi
authors.forename: R V
authors.initials: RV
authors.lastname: Omkumar
mesh_terms: D000818:Animals; D008297:Male; D010766:Phosphorylation; D057907:Post-Synaptic Density / Q000378:metabolism*; D016548:Prosencephalon / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D054645:Protein Phosphatase 1 / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000378:metabolism*; D012694:Serine / Q000378:metabolism*
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D011493:Protein Kinase C; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2