A Novel Interacting Protein SERP1 Regulates the N-Linked Glycosylation and Function of GLP-1 Receptor in the Liver

作者：Xiao, Yuanyuan; Han, Junfeng; Wang, Qianqian; Mao, Yueqin; Wei, Meilin; Jia, Weiping; Wei, Li^*

来源：Journal of Cellular Biochemistry, 2017, 118(11): 3616-3626.

DOI：10.1002/jcb.26207

• STRESS-ASSOCIATED ENDOPLASMIC RETICULUM PROTEIN 1
• GLUCAGON-LIKE PEPTIDE 1 RECEPTOR
• GLYCOSYLATION
• G PROTEIN-COUPLED RECEPTOR

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.

• 出版日期2017-11
• 单位上海市临床检验中心; 上海交通大学