Abstract
The glutamate receptor δ2 subunit (GluRδ2) is selectively expressed in cerebellar Purkinje neurons (PNs) and is involved in the long-term depression (LTD). However, little is known about the mechanism of its action. Acute expression of the wild-type GluRδ2 in the GluRδ2-deficient PN rescued the LTD induction, suggesting the direct role of GluRδ2 in LTD. To identify the critical region of GluRδ2 necessary for the LTD induction, we constructed and expressed various mutant GluRδ2 proteins in the GluRδ2-deficient PNs. The mutant GluRδ2 possessing the membrane-proximal 21 amino acid residues (AAs) in C-terminal cytoplasmic region rescued the LTD induction, whereas the mutant with membrane-proximal 13 AAs failed. In addition, overexpression of the membrane-proximal 14-20 AAs fused to EGFP suppressed the LTD induction in a wild type PN. These results suggest that the membrane-proximal 14-20 AAs of GluRδ2 plays an essential role in LTD. Then, we identified protein interacting with C kinase 1 (PICK1) as a molecule interacting with the membrane-proximal C-terminal region of GluRδ2 by yeast two-hybrid screening. PICK1 co-localized with GluRδ2 at spines of PNs, and immunoprecipitation assays showed that GluRδ2 bound to PICK1 mainly through the membrane-proximal 14-20 AAs. These results indicate that the membrane-proximal 14-20 AAs of GluRδ2 are essential for both LTD and interaction with PICK1, and suggest that interaction between GluRδ2 and PICK1 might be critical for the LTD induction. [J Physiol Sci. 2006;56 Suppl:S168]
