Introduction
Classical GPCR signaling models assumed uniform receptor distribution and immediate signal termination upon ligand dissociation. Contemporary research reveals that subcellular location and temporal dynamics fundamentally determine signaling outcomes. This session examines how receptor nanodomains, endosomal signaling compartments, and biomolecular condensates create distinct signaling environments that prevent crosstalk and enable pathway specificity.
The discussion spans location bias mechanisms that drive differential G protein versus arrestin activation, advanced imaging techniques that visualize these spatiotemporal processes, and the emerging role of liquid-liquid phase separation in organizing signaling complexes. Designed for structural pharmacologists, cell biologists, and drug discovery scientists working on GPCR systems where spatial organization influences therapeutic outcomes.
Instructor
Sudarshan Rajagopal is Associate Professor of Medicine in the Division of Cardiology at Duke University School of Medicine and Co-Director of the Duke Pulmonary Vascular Disease Center.
His research has fundamentally advanced understanding of receptor regulatory mechanisms underlying cardiovascular and inflammatory diseases, particularly pulmonary hypertension. Since establishing his independent laboratory, his group has made defining contributions to biased agonism mechanisms and chemokine system signaling, with particular expertise in how spatial organization influences GPCR function in disease contexts.
His work on spatiotemporal GPCR regulation directly informs the mechanistic framework addressed in this Masterclass.
