Endogenous cell membrane interactome mapping for the GLP-1 receptor in different cell types

IF 12.9 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ting Dang, Jie Yu, Zhihe Cao, Bingjie Zhang, Shanshan Li, Ye Xin, Lingyun Yang, Ronghui Lou, Min Zhuang, Wenqing Shui
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Abstract

The GLP-1 receptor, one of the most successful drug targets for the treatment of type 2 diabetes and obesity, is known to engage multiple intracellular signaling proteins. However, it remains less explored how the receptor interacts with proteins on the cell membrane. Here, we present a ligand-based proximity labeling approach to interrogate the native cell membrane interactome for the GLP-1 receptor after agonist simulation. Our study identified several unreported putative cell membrane interactors for the endogenous receptor in either a pancreatic β cell line or a neuronal cell line. We further uncovered new regulators of GLP-1 receptor-mediated signaling and insulinotropic responses in β cells. Additionally, we obtained a time-resolved cell membrane interactome map for the receptor in β cells. Therefore, our study provides a new approach that is generalizable to map endogenous cell membrane interactomes for G-protein-coupled receptors to decipher the molecular basis of their cell-type-specific functional regulation.

Abstract Image

不同细胞类型中 GLP-1 受体的内源性细胞膜相互作用组图谱
GLP-1 受体是治疗 2 型糖尿病和肥胖症最成功的药物靶点之一,已知它能与多种细胞内信号蛋白相互作用。然而,人们对该受体如何与细胞膜上的蛋白相互作用的探索仍然较少。在这里,我们介绍了一种基于配体的近似标记方法,以探究GLP-1受体在激动剂模拟后的原生细胞膜相互作用组。我们的研究在胰腺β细胞系或神经元细胞系中发现了几种未报道的内源性受体的细胞膜相互作用体。我们还发现了 GLP-1 受体介导的信号传导和β细胞中促胰岛素反应的新调节因子。此外,我们还获得了β细胞中受体的时间分辨细胞膜相互作用组图。因此,我们的研究提供了一种新的方法,可用于绘制G蛋白偶联受体的内源性细胞膜相互作用组图,以破译其细胞类型特异性功能调控的分子基础。
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来源期刊
Nature chemical biology
Nature chemical biology 生物-生化与分子生物学
CiteScore
23.90
自引率
1.40%
发文量
238
审稿时长
12 months
期刊介绍: Nature Chemical Biology stands as an esteemed international monthly journal, offering a prominent platform for the chemical biology community to showcase top-tier original research and commentary. Operating at the crossroads of chemistry, biology, and related disciplines, chemical biology utilizes scientific ideas and approaches to comprehend and manipulate biological systems with molecular precision. The journal embraces contributions from the growing community of chemical biologists, encompassing insights from chemists applying principles and tools to biological inquiries and biologists striving to comprehend and control molecular-level biological processes. We prioritize studies unveiling significant conceptual or practical advancements in areas where chemistry and biology intersect, emphasizing basic research, especially those reporting novel chemical or biological tools and offering profound molecular-level insights into underlying biological mechanisms. Nature Chemical Biology also welcomes manuscripts describing applied molecular studies at the chemistry-biology interface due to the broad utility of chemical biology approaches in manipulating or engineering biological systems. Irrespective of scientific focus, we actively seek submissions that creatively blend chemistry and biology, particularly those providing substantial conceptual or methodological breakthroughs with the potential to open innovative research avenues. The journal maintains a robust and impartial review process, emphasizing thorough chemical and biological characterization.
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