Binding of glutamate receptor delta2 to its scaffold protein, Delphilin, is regulated by PKA.
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.
Sonoda
Tomoko
T
Department of Molecular Biodefence Research, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Mochizuki
Chieko
C
Yamashita
Tetsuji
T
Watanabe-Kaneko
Keiko
K
Miyagi
Yohei
Y
Shigeri
Yasushi
Y
Yazama
Futoshi
F
Okuda
Kenji
K
Kawamoto
Susumu
S
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*
D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; C447759:delphilin; C107913:glutamate receptor delta 2; D017868:Cyclic AMP-Dependent Protein Kinases