A sensitive biosensor of endogenous Gα_i activity enables the accurate characterization of endogenous GPCR agonist responses.

ABSTRACT: The activation of heterotrimeric G proteins (Gαβγ) by G protein-coupled receptors (GPCRs) is a mechanism broadly used by eukaryotes to transduce signals across the plasma membrane and a target for many clinical drugs. Many optical biosensors commonly used for measuring GPCR-stimulated G protein activity rely on exogenously expressed GPCRs and/or G proteins, which compromise readout fidelity. Biosensors that measure endogenous signaling may interfere with the signaling process under investigation or have a limited dynamic range of detection, hindering applicability. Here, we developed an optical BRET-based biosensor, Gα_i bONE-GO, that detects endogenous GTP-bound (active) Gα_i upon stimulation of endogenous GPCRs more robustly than existing sensors of endogenous activit

SUBMITTER: Luebbers A 

PROVIDER: S-EPMC12077488 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature