CGRP Receptor Signalling Pathways
CGRP Receptor Signalling Pathways
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DOI：
10.1007/164_2018_130
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发表时间：
2019-01-01
期刊：
影响因子：
--
通讯作者：
Cottrell, Graeme S.
中科院分区：
文献类型：
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作者：
Cottrell, Graeme S.
降钙素基因相关肽（CGRP）是一种混杂肽，类似于降钙素肽家族的许多其他成员。CGRP对许多不同受体具有不同的亲和力和功效，这使得破译CGRP受体的信号传导对研究人员来说是一项具有挑战性的任务。尽管它不是典型的G蛋白偶联受体（GPCR），因为它不仅仅由GPCR组成，但CGRP受体激活许多与其他GPCR相同的信号传导途径。这包括G蛋白家族和各种蛋白激酶和转录因子。现在还清楚的是，除了启动细胞表面的信号，GPCR，包括CGRP受体，也激活不同的信号转导途径，因为受体是运输沿着内吞conduil.GPCR的特性激活多个，我们将首先考虑降钙素受体样受体（CGRP）和受体活性修饰蛋白1（RAMP 1）的复合物作为CGRP受体。我们将讨论CGRP受体成分的发现，控制其内在化和内吞后运输（回收和降解）的分子机制，以及该受体在模型细胞系中引起的各种信号级联反应。然后，我们将讨论CGRP介导的信号通路在原代细胞相关的偏头痛，包括神经元，神经胶质细胞和血管平滑肌celles.Investigation的所有CGRP和CGRP受体介导的信号级联是至关重要的，如果我们要充分了解CGRP在偏头痛中的作用，无疑将发掘新的目标偏头痛和其他CGRP驱动的疾病的治疗。
Calcitonin gene-related peptide (CGRP) is a promiscuous peptide, similar to many other members of the calcitonin family of peptides. The potential of CGRP to act on many different receptors with differing affinities and efficacies makes deciphering the signalling from the CGRP receptor a challenging task for researchers.Although it is not a typical G protein-coupled receptor (GPCR), in that it is composed not just of a GPCR, the CGRP receptor activates many of the same signalling pathways common for other GPCRs. This includes the family of G proteins and a variety of protein kinases and transcription factors. It is now also clear that in addition to the initiation of cell-surface signalling, GPCRs, including the CGRP receptor, also activate distinct signalling pathways as the receptor is trafficking along the endocytic conduit.Given CGRP's characteristic of activating multiple GPCRs, we will first consider the complex of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) as the CGRP receptor. We will discuss the discovery of the CGRP receptor components, the molecular mechanisms controlling its internalization and post-endocytic trafficking (recycling and degradation) and the diverse signalling cascades that are elicited by this receptor in model cell lines. We will then discuss CGRP-mediated signalling pathways in primary cells pertinent to migraine including neurons, glial cells and vascular smooth muscle cells.Investigation of all the CGRP- and CGRP receptor-mediated signalling cascades is vital if we are to fully understand CGRP's role in migraine and will no doubt unearth new targets for the treatment of migraine and other CGRP-driven diseases.