Distinct Patterns of Internalization of Different Calcitonin GeneRelated Peptide Receptors
Gingell, Joseph J; Rees, Tayla A; Hendrikse, Erica R; Siow, Andrew; Rennison, David; Scotter, John; Harris, Paul W R; Brimble, Margaret A; Walker, Christopher S; Hay, Debbie L
Calcitonin gene-related peptide (CGRP) is a neuropeptide that is involved in the transmission of pain. Drugs targeting CGRP or a CGRP receptor are efficacious in the treatment of migraine. The canonical CGRP receptor is a complex of a G protein-coupled receptor, the calcitonin-like receptor (CLR), with an accessory protein, receptor activity-modifying protein 1 (RAMP1). A second receptor, the AMY1 receptor, a complex of the calcitonin receptor with RAMP1, is a dual high-affinity receptor for CGRP and amylin. Receptor regulatory processes, such as internalization, are crucial for controlling peptide and drug responsiveness. Given the importance of CGRP receptor activity in migraine we compared the internalization profiles of both receptors for CGRP using novel fluorescent probes and a combination of live cell imaging, fixed cell imaging, and ELISA. This revealed stark differences in the regulation of each receptor with the AMY1 receptor unexpectedly showing little internalization.
Publisher: ACS Publications
Published in: ACS Pharmacology & Translational Science, volume 3, issue 2
Rights Statement: This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Pharmacology & Translational Science, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsptsci.9b00089
Keywords: amylin; CGRP; GPCR; internalization; migraine; receptor activity-modifying protein
Research Type: Journal Article