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

Area of Science:

• Biochemistry
• Cell Biology
• Pharmacology

Background:

• The Glucagon-like peptide-1 (GLP-1) receptor is a key therapeutic target for type 2 diabetes and obesity.
• While intracellular signaling is well-studied, the GLP-1 receptor's cell membrane protein interactions remain largely unexplored.

Purpose of the Study:

• To investigate the native cell membrane interactome of the GLP-1 receptor upon agonist stimulation.
• To identify novel regulators of GLP-1 receptor signaling and insulin secretion in pancreatic beta cells.
• To develop a generalizable method for mapping G-protein-coupled receptor (GPCR) cell membrane interactomes.

Main Methods:

• Utilized a ligand-based proximity labeling technique to probe the cell membrane interactome.
• Applied the method to pancreatic beta cell and neuronal cell lines.
• Generated a time-resolved map of the GLP-1 receptor's cell membrane interactions.

Main Results:

• Identified several previously unreported putative cell membrane interactors for the endogenous GLP-1 receptor.
• Discovered new regulators involved in GLP-1 receptor-mediated signaling and insulinotropic effects in beta cells.
• Characterized a dynamic, time-resolved map of the receptor's membrane environment.

Conclusions:

• The study presents a novel proximity labeling approach to map endogenous GPCR cell membrane interactomes.
• This methodology can elucidate the molecular mechanisms underlying cell-type-specific GPCR functions.
• Findings contribute to a deeper understanding of GLP-1 receptor biology and its therapeutic potential.