GPCRs in health and disease
Kathleen M. Caron, University of North Carolina at Chapel Hill, USA
Illuminating Orphan GPCRs in Cardiovascular Development and Function
Since approximately 30% of all clinically-available drugs target G-protein coupled receptors (GPCRs), there is great interest in learning more about this family of proteins in order to discover new therapeutic targets. When considering the different classes of proteins encoded by the human genome that are predicted to be pharmacologically-tractable, a remarkable one quarter represent GPCRs. And yet, of the ~345 non-odorant GPCRs a large proportion remain orphan—with no known ligand—or have uncharacterized physiological functions. Since we have a dearth of pharmacological targets for lymphatic vessels, it stands to reason that focused efforts to explore and characterize the lymphatic “GPCRome” is a worthwhile endeavor. Using multimodal genomic approaches, we have identified 4 orphan GPCRs that have enriched expression in lymphatic endothelial cells: GPRC5B, GPR116, FZD8 and GPR61. Using cell-based and model organism approaches we have characterized the expression and functions of these receptors in the lymphatic vasculature during development and adulthood. Our results provide novel physiological insights into several orphan GPCRs and have the potential to illuminate therapeutic targets for the modulation of lymphatics, which remains an understudied research area with unmet clinical needs.
Location Bias in cAMP and PTHR Biology
Structure-function effects of a disease-linked variant of the oxytocin receptor