The functions and signalling mechanisms of the Ang-(1–7) [angiotensin-(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 (postsynaptic density 95), a novel binding protein of Mas receptor, was identified, and their association was characterized further. Mas specifically interacts with PDZ1-2, but not the PDZ3, domain of PSD95 via Mas-CT (Mas C-terminus), and the last four amino acids [ETVV (Glu-Thr-Val-Val)] of Mas-CT were determined to be essential for this interaction, as shown by GST pull-down, co-immunoprecipitation and confocal co-localization 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 binds directly to Mas, blocking the ubiquitination and subsequent degradation of the receptor via the ubiquitin–proteasome proteolytic pathway.
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Research Article|
July 12 2013
Stabilization of the angiotensin-(1–7) receptor Mas through interaction with PSD95
Weihua Bian;
Weihua Bian
1
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Licui Sun;
Licui Sun
1
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Longyan Yang;
Longyan Yang
1
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Ji-Feng Li;
Ji-Feng Li
2
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Jia Hu;
Jia Hu
†Proteomic Research Center, Capital Medical University, Beijing 100069, China
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Shuai Zheng;
Shuai Zheng
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Ruihan Guo;
Ruihan Guo
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Duiping Feng;
Duiping Feng
‡Department of Radiology, First Hospital of Shanxi Medical University, Taiyuan 030001, China
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Qian Ma;
Qian Ma
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Xiaocui Shi;
Xiaocui Shi
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Ying Xiong;
Ying Xiong
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Xiaomei Yang;
Xiaomei Yang
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Ran Song;
Ran Song
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
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Jianguo Xu;
Jianguo Xu
§Shaoxing Second Hospital, Zhejiang 312000, China
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Songlin Wang;
Songlin Wang
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
∥Molecular Laboratory for Gene Therapy and Tooth Regeneration, Capital Medical University School of Stomatology, Beijing 100050, China
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Junqi He
Junqi He
3
*Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing 100069, China
†Proteomic Research Center, Capital Medical University, Beijing 100069, China
3To whom correspondence should be addressed (email jq_he@ccmu.edu.cn).
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Publisher: Portland Press Ltd
Received:
December 19 2012
Revision Received:
May 24 2013
Accepted:
May 24 2013
Accepted Manuscript online:
May 24 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 453 (3): 345–356.
Article history
Received:
December 19 2012
Revision Received:
May 24 2013
Accepted:
May 24 2013
Accepted Manuscript online:
May 24 2013
Citation
Weihua Bian, Licui Sun, Longyan Yang, Ji-Feng Li, Jia Hu, Shuai Zheng, Ruihan Guo, Duiping Feng, Qian Ma, Xiaocui Shi, Ying Xiong, Xiaomei Yang, Ran Song, Jianguo Xu, Songlin Wang, Junqi He; Stabilization of the angiotensin-(1–7) receptor Mas through interaction with PSD95. Biochem J 1 August 2013; 453 (3): 345–356. doi: https://doi.org/10.1042/BJ20121885
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