Stabilization of the Angiotensin-(1-7) Receptor Mas through Interaction with PSD95

The functions and signaling mechanisms of the angiotensin-(1-7) (Ang-(1-7)) receptor Mas have been studied extensively. However, less attention has been paid to the intracellular regulation of Mas protein. In the present study, PSD95, a novel binding protein of Mas receptor was identified, and their association was further characterized. Mas specifically interacts with the PDZ1-2 but not the PDZ3 domain of PSD95 via Mas carboxyl terminus (Mas-CT), and the last four amino acids (ETVV) of Mas-CT were determined to be essential for this interaction, as shown by the results of GST pull-down, Co-IP and confocal colocalization experiments. Gain-of-function and loss-of-function studies indicated that PSD95 enhanced Mas protein expression by increasing the stabilization of the receptor. Mas degradation was robustly inhibited by the proteasome inhibitor MG132 in time and dose-dependent manners, and the expression of PSD95 impaired Mas ubiquitination, indicating that the PSD95/Mas association inhibits Mas receptor degradation via the ubiquitin-proteasome proteolytic pathway.
These findings reveal a novel mechanism of Mas receptor regulation by which its expression is modulated at the post-translational level by ubiquitination, and clarify the role of PSD95, which directly binds to Mas, blocking the ubiquitination and subsequent degradation of the receptor via the ubiquitin-proteasome proteolytic pathway.

Source: BJ Signal - May 24, 2013 Category: Biochemistry Authors: W Bian, L Sun, L Yang, J Li, J Hu, S Zheng, R Guo, D Feng, Q Ma, X Shi, Y Xiong, X Yang, R Song, J Xu, S Wang, J He Tags: BJ Signal Source Type: research