Binding of glutamate receptor δ2 to its scaffold protein, Delphilin, is regulated by PKA

The glutamate receptor delta 2 (GluR delta 2) 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 GluR delta 2-interacting protein, selectively expressed in Purkinje cell-parallel fiber synapses, and specifically interacts with the GluR delta 2 C-terminus via its PDZ domain. Here, surface plasmon resonance analyses showed that Delphilin PDZ bound to GluR delta 2 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 GluR delta 2 C-terminus by cAMP-dependent protein kinase (PKA) in vitro. In the experiments using heterologous expression system, Delphilin commumoprecipitated with GluR delta 2 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 GluR delta 2 C-terminus by PKA may regulate the binding of GluR delta 2 to its scaffolding protein, Delphilin. (c) 2006 Elsevier Inc. All rights reserved.