期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 118, 期 11, 页码 3616-3626出版社
WILEY
DOI: 10.1002/jcb.26207
关键词
STRESS-ASSOCIATED ENDOPLASMIC RETICULUM PROTEIN 1; GLUCAGON-LIKE PEPTIDE 1 RECEPTOR; GLYCOSYLATION; G PROTEIN-COUPLED RECEPTOR
资金
- Shanghai Jiao Tong University Wuxi Research Institute [2011JDZX021]
- National Natural Science Foundation of China [81200564, 81370956]
Glucagon-like peptide 1 (GLP-1) exerts multiple effects on metabolism through its receptor, GLP-1R, in the liver. Activation and transduction of GLP-1R require complex interactions of largely unknown accessory proteins, and these processes are crucial to the response to endoplasmic reticulum (ER) stress. Using the membrane-based split ubiquitin yeast two-hybrid system (MYTH) and a human liver cDNA library, we obtained the human GLP-1R interactome and identified SERP1 as a potential interacting protein based on its ability to stabilize membrane proteins and facilitate N-linked glycosylation. GLP-1R and SERP1 were co-expressed in HEK-293 cells, and their interaction was confirmed by co-immunoprecipitation. We then found that overexpression of SERP1 could rescue GLP-1R glycosylation after application of tunicamycin to block N-linked glycosylation. SERP1 overexpression also attenuated exendin-4-stimulated cAMP accumulation and AMPK activation. However, the glycosylation and function of mutant GLP-1R, in which all three sites for N-linked glycosylation were mutated, were not increased with overexpression of SERP1. Moreover, as a GLP-1R interactor, SERP1 could also partly reverse the accumulation of tunicamycin-induced ER stress. Taken together, our findings identify a group of proteins that interact with GLP-1R and show that one specific interacting protein, SERP1, has an important role in facilitating the glycosylation of GLP-1R and rescuing its activities after ER stress induced by tunicamycin. J. Cell. Biochem. 118: 3616-3626, 2017. (c) 2017 Wiley Periodicals, Inc.
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