Spatiotemporal dynamics of β-arrestin-mediated Src activation in 5-HT7 receptor signaling pathway - PubMed
4 hours ago
- #β-arrestin
- #GPCR
- #5-HT7R
- GPCRs initiate G protein-mediated signaling pathways and are desensitized via β-arrestin-dependent internalization.
- β-arrestin also mediates G protein-independent signaling pathways, leading to distinct cellular responses.
- GPCR-biased ligands selectively modulate G protein- or β-arrestin-dependent pathways for drug discovery.
- Biased ligands for 5-HT7R were developed, with G protein-biased ligand (2b) inducing ASD behavior in mice.
- β-arrestin-biased ligand (1g) induced slow but sustained activation of Src via β-arrestin-2 recruitment.
- Src was recruited to 5-HT7R via β-arrestin-2, followed by receptor internalization and endosomal accumulation.
- Sustained colocalization of Src at internalized receptor complex explains slow and sustained Src activation.
- Findings highlight spatiotemporal regulation of Src activation in GPCR-biased signaling pathways.