上海科技大学知识管理系统

["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 beta cell line or a neuronal cell line. We further uncovered new regulators of GLP-1 receptor-mediated signaling and insulinotropic responses in beta cells. Additionally, we obtained a time-resolved cell membrane interactome map for the receptor in beta 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.","Development of a ligand-based proximity labeling strategy enables interrogation of the native cell membrane interactome for the GLP-1 receptor in two cell types, revealing new regulators of receptor-mediated signaling and beta cell responses."]