Optical tools for visualizing and controlling human GLP-1 receptor activation with high spatiotemporal resolution.

ABSTRACT: The glucagon-like peptide-1 receptor (GLP1R) is a broadly expressed target of peptide hormones with essential roles in energy and glucose homeostasis, as well as of the blockbuster weight-loss drugs semaglutide and liraglutide. Despite its large clinical relevance, tools to investigate the precise activation dynamics of this receptor with high spatiotemporal resolution are limited. Here, we introduce a novel genetically encoded sensor based on the engineering of a circularly permuted green fluorescent protein into the human GLP1R, named GLPLight1. We demonstrate that fluorescence signal from GLPLight1 accurately reports the expected receptor conformational activation in response to pharmacological ligands with high sensitivity (max ΔF/F₀=528%) and temporal resolution (τ_ON</

SUBMITTER: Duffet L 

PROVIDER: S-EPMC10262203 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature