|
|||||
|
|
A novel association of mGluR1a with the PDZ scaffold protein CAL modulates receptor activity |
|
| Authors: | Jiuqin Zhang Shan Cheng Yanmei Ma Dali Luo Hong Zhang Junqi He |
| Affiliation: | a Department of Biochemistry and Molecular Biology, Capital Medical University, No. 10 Xitoutiao, You An Men, Beijing 100069, China b Department of Cell Biology, Capital Medical University, Beijing 100069, China c Department of Pharmacology, Capital Medical University, Beijing 100069, China d Allen Institute for Brain Science, Seattle, WA 98103, USA |
| Abstract: | Metabotropic glutamate receptor subtype 1a (mGluR1a) associates with the proteins mediating its receptor activity, suggesting a complex-controlled function of mGluR1a. Here, using glutathione-S-transferase pull-down, co-immnoprecipitation and immnoflurescence assays in vitro and in vivo, we have found CFTR-associated ligand (CAL) to be a novel binding partner of mGluR1a, through its PSD95/discslarge/ZO1homology domain. Deletion of mGluR1a-carboxyl terminus (CT) or mutation of Leu to Ala in the CT of mGluR1a reduces the association, indicating the essential binding region of mGluR1a for CAL. Functionally, the interaction of mGluR1a with CAL was shown to inhibit mGluR1a-mediated ERK1/2 activation, without an apparent effect, via the C-terminal-truncated receptor. These findings might provide a novel mechanism for the regulation of mGluR1a-mediated signaling through the interaction with CAL. Structured summary
|
| Keywords: | PDZ, PSD95/discslarge/ZO1homology mGluR1a, metabotropic glutamate receptor subtype 1a GST, glutathione-S-transferase CT, carboxyl terminus ΔCT, deleted carboxyl terminus His, hexahistidinetagged HRP, horseradish peroxidase SDS, sodium dodecyl sulfate PAGE, polyacrylamide gel electrophoresis WT, wild-type HA, hemagglutinin CAL, CFTR-associated ligand |
| 本文献已被 ScienceDirect 等数据库收录！ | |