title: Binding of glutamate receptor delta2 to its scaffold protein, Delphilin, is regulated by PKA.
abstract: The glutamate receptor delta2 (GluRdelta2) is selectively expressed in cerebellar Purkinje cells and plays an important role in motor learning, motor coordination, and long-term depression. Delphilin is identified as a GluRdelta2-interacting protein, selectively expressed in Purkinje cell-parallel fiber synapses, and specifically interacts with the GluRdelta2 C-terminus via its PDZ domain. Here, surface plasmon resonance analyses showed that Delphilin PDZ bound to GluRdelta2 C-terminal peptide (DPDRGTSI), but not to its phosphopeptides (DPDRGphosphoTSI and DPDRGTphosphoSI). We showed the incorporation of phosphate into threonine at -2 (-2T) and serine at -1 (-1S) of GluRdelta2 C-terminus by cAMP-dependent protein kinase (PKA) in vitro. In the experiments using heterologous expression system, Delphilin coimmunoprecipitated with GluRdelta2 was dramatically decreased under the condition with forskolin and isobutylmethylxanthine, which led to cAMP-dependent phosphorylation by PKA. Thus, phosphorylation of -2T and/or -1S of GluRdelta2 C-terminus by PKA may regulate the binding of GluRdelta2 to its scaffolding protein, Delphilin.
authors.affiliation: Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Sonoda
authors.forename: Chieko
authors.initials: C
authors.lastname: Mochizuki
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Yamashita
authors.forename: Keiko
authors.initials: K
authors.lastname: Watanabe-Kaneko
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shigeri
authors.forename: Futoshi
authors.initials: F
authors.lastname: Yazama
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuda
authors.forename: Susumu
authors.initials: S
authors.lastname: Kawamoto
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017470:Receptors, Glutamate / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; C447759:delphilin; C107913:glutamate receptor delta 2; D017868:Cyclic AMP-Dependent Protein Kinases