Department of Endocrinology and Diabetes, First Floor, C Block, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands 6009, Western Australia, Australia.
Endocr Rev. 2011 Feb;32(1):3-30. doi: 10.1210/er.2009-0043. Epub 2010 Aug 20.
Compelling evidence of a cell surface receptor sensitive to extracellular calcium was observed as early as the 1980s and was finally realized in 1993 when the calcium-sensing receptor (CaR) was cloned from bovine parathyroid tissue. Initial studies relating to the CaR focused on its key role in extracellular calcium homeostasis, but as the amount of information about the receptor grew it became evident that it was involved in many biological processes unrelated to calcium homeostasis. The CaR responds to a diverse array of stimuli extending well beyond that merely of calcium, and these stimuli can lead to the initiation of a wide variety of intracellular signaling pathways that in turn are able to regulate a diverse range of biological processes. It has been through the examination of the molecular characteristics of the CaR that we now have an understanding of how this single receptor is able to convert extracellular messages into specific cellular responses. Recent CaR-related reviews have focused on specific aspects of the receptor, generally in the context of the CaR's role in physiology and pathophysiology. This review will provide a comprehensive exploration of the different aspects of the receptor, including its structure, stimuli, signalling, interacting protein partners, and tissue expression patterns, and will relate their impact on the functionality of the CaR from a molecular perspective.
早在 20 世纪 80 年代，就观察到了一种对细胞外钙敏感的细胞表面受体的有力证据，直到 1993 年，从牛甲状旁腺组织中克隆出钙敏感受体 (CaR) 后，这一证据最终得到证实。最初的 CaR 研究主要集中在其在细胞外钙稳态中的关键作用上，但随着有关受体的信息量增加，很明显它参与了许多与钙稳态无关的生物学过程。CaR 对多种多样的刺激作出反应，这些刺激远远超出了钙的范围，这些刺激可以启动多种不同的细胞内信号通路，进而能够调节多种不同的生物学过程。正是通过对 CaR 的分子特征进行研究，我们现在才了解到这个单一受体是如何将细胞外信息转化为特定的细胞反应的。最近与 CaR 相关的综述主要集中在受体的特定方面，通常是在 CaR 在生理学和病理生理学中的作用的背景下。这篇综述将全面探讨受体的不同方面，包括其结构、刺激、信号转导、相互作用的蛋白伴侣以及组织表达模式，并从分子角度探讨它们对 CaR 功能的影响。
