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原发性纤毛中的信号转导 - 分析和操纵 GPCR 和第二信使信号转导。

Signal transduction in primary cilia - analyzing and manipulating GPCR and second messenger signaling.

机构信息

Institute of Innate Immunity, Biophysical Imaging, Medical Faculty, University of Bonn, 53127 Bonn, Germany.

Center for Molecular Signaling (PZMS), Center of Human and Molecular Biology (ZHMB), Saarland University, School of Medicine, 66421 Homburg, Germany.

出版信息

Pharmacol Ther. 2021 Aug;224:107836. doi: 10.1016/j.pharmthera.2021.107836. Epub 2021 Mar 18.

Abstract

The primary cilium projects from the surface of most vertebrate cells, where it senses extracellular signals to regulate diverse cellular processes during tissue development and homeostasis. Dysfunction of primary cilia underlies the pathogenesis of severe diseases, commonly referred to as ciliopathies. Primary cilia contain a unique protein repertoire that is distinct from the cell body and the plasma membrane, enabling the spatially controlled transduction of extracellular cues. G-protein coupled receptors (GPCRs) are key in sensing environmental stimuli that are transmitted via second messenger signaling into a cellular response. Here, we will give an overview of the role of GPCR signaling in primary cilia, and how ciliary GPCR signaling can be targeted by pharmacology, chemogenetics, and optogenetics.

摘要

纤毛从大多数脊椎动物细胞的表面伸出,在那里它可以感知细胞外信号,从而在组织发育和稳态过程中调节各种细胞过程。纤毛的功能障碍是严重疾病(通常称为纤毛病)的发病基础。初级纤毛含有独特的蛋白质组,与细胞体和质膜不同,能够实现细胞外线索的空间控制转导。G 蛋白偶联受体(GPCR)是感应环境刺激的关键,这些刺激通过第二信使信号传递到细胞反应中。在这里,我们将概述 GPCR 信号在初级纤毛中的作用,以及纤毛 GPCR 信号如何被药理学、化学生物学和光遗传学靶向。

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