<p>Agonist bias occurs when different ligands produce distinct signalling outputs when acting at the same receptor. However, its physiological relevance is not always clear. Using primary human cells and gene editing techniques, we demonstrate endogenous agonist bias with physiological consequences for the calcitonin receptor-like receptor, CLR. By switching the receptor-activity modifying protein (RAMP) associated with CLR we can “re-route” the physiological pathways activated by endogenous agonists calcitonin gene-related peptide (CGRP), adrenomedullin (AM) and adrenomedullin 2 (AM2). AM2 promotes calcium-mediated nitric oxide signalling whereas CGRP and AM show pro-proliferative effects in cardiovascular cells, thus providing a rationale for the expression of the three peptides. CLR-based agonist bias occurs naturally in human cells and has a fundamental purpose for its existence. We anticipate this will be a starting point for more studies into RAMP function in native environments and their importance in endogenous GPCR signalling.</p>

doi.org/10.1038/s42003-021-02293-w, hdl.handle.net/1765/136038
Research Evaluation
Erasmus School of Health Policy & Management (ESHPM)

AL (Annette) Boaz, RAJ (Robert) Borst, M (Maarten) Kok, & A O'Shea. (2021). How far does an emphasis on stakeholder engagement and co-production in research present a threat to academic identity and autonomy? A prospective study across five European countries. Research Evaluation. doi:10.1093/reseval/rvab013