不同降钙素基因相关肽受体的内化独特模式
Distinct Patterns of Internalization of Different Calcitonin Gene-Related Peptide Receptors.
作者信息
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
机构信息
School of Biological Sciences, University of Auckland, Auckland 1142, New Zealand.
Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1142, New Zealand.
出版信息
ACS Pharmacol Transl Sci. 2020 Feb 26;3(2):296-304. doi: 10.1021/acsptsci.9b00089. eCollection 2020 Apr 10.
Abstract
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 AMY 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 AMY receptor unexpectedly showing little internalization.
摘要
降钙素基因相关肽（CGRP）是一种参与疼痛传递的神经肽。靶向CGRP或CGRP受体的药物在偏头痛治疗中有效。经典的CGRP受体是一种G蛋白偶联受体——降钙素样受体（CLR）与一种辅助蛋白——受体活性修饰蛋白1（RAMP1）形成的复合物。第二种受体，即AMY受体，是降钙素受体与RAMP1形成的复合物，是一种对CGRP和胰淀素具有双重高亲和力的受体。受体调节过程，如内化，对于控制肽和药物反应性至关重要。鉴于CGRP受体活性在偏头痛中的重要性，我们使用新型荧光探针以及活细胞成像、固定细胞成像和酶联免疫吸附测定相结合的方法，比较了两种CGRP受体的内化情况。这揭示了每种受体调节方面的显著差异，其中AMY受体出人意料地几乎没有内化。
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