科研之友
微信
新浪微博
Facebook
分享链接
摘要
The glutamate receptor delta 2 subunit (GluR delta 2) 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 GluR delta 2 in the GluR delta 2-deficient PN rescued the induction of LTD, suggesting the direct role of GluR delta 2 in LTD. To identify the critical region of GluR delta 2 necessary for LTD, we constructed and expressed various mutant GluR delta 2 proteins in the GluR delta 2-deficient PNs. The mutant GluR delta 2 possessing the membrane-proximal 21 aa residues in the C-terminal cytoplasmic region rescued the induction of LTD, whereas the mutant with membrane-proximal 13 aa failed. In addition, overexpression of 865 similar to 871 aa of GluR delta 2 (corresponding to membrane-proximal 14 similar to 20 aa) fused to EGFP (enhanced green fluorescent protein) suppressed LTD in a wild-type PN. These results suggest that 865 similar to 871 aa of GluR delta 2 play an essential role in LTD. We next identified protein interacting with C kinase 1 (PICK1) as a molecule interacting with the membrane-proximal C-terminal region of GluR delta 2 by yeast two-hybrid screening. PICK1 plays an essential role in LTD. It colocalized with GluR delta 2 at spines of PNs, and immunoprecipitation assays showed that GluR delta 2 bound to PICK1 mainly through 865 similar to 871 aa. These results indicate that 865 similar to 871 aa of GluR delta 2 are essential for both LTD and interaction with PICK1, and suggest that interaction between GluR delta 2 and PICK1 might be critical for the induction of LTD.
- 出版日期2006-4-5
