Direct interrogation of context-dependent GPCR activity with a universal biosensor platform.
Cell
; 187(6): 1527-1546.e25, 2024 Mar 14.
Article
en En
| MEDLINE
| ID: mdl-38412860
ABSTRACT
G protein-coupled receptors (GPCRs) are the largest family of druggable proteins encoded in the human genome, but progress in understanding and targeting them is hindered by the lack of tools to reliably measure their nuanced behavior in physiologically relevant contexts. Here, we developed a collection of compact ONE vector G-protein Optical (ONE-GO) biosensor constructs as a scalable platform that can be conveniently deployed to measure G-protein activation by virtually any GPCR with high fidelity even when expressed endogenously in primary cells. By characterizing dozens of GPCRs across many cell types like primary cardiovascular cells or neurons, we revealed insights into the molecular basis for G-protein coupling selectivity of GPCRs, pharmacogenomic profiles of anti-psychotics on naturally occurring GPCR variants, and G-protein subtype signaling bias by endogenous GPCRs depending on cell type or upon inducing disease-like states. In summary, this open-source platform makes the direct interrogation of context-dependent GPCR activity broadly accessible.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Técnicas Biosensibles
/
Transducción de Señal
Límite:
Humans
Idioma:
En
Revista:
Cell
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos