Pharmacology of ORAI channels as a tool to understand their physiological functions.
Pharmacology of ORAI channels as a tool to understand their physiological functions.
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DOI：
10.1586/ecp.10.23
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发表时间：
2010-05-01
影响因子：
4.4
通讯作者：
Peinelt, Christine
中科院分区：
文献类型：
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作者：
Bogeski, Ivan;Al-Ansary, Dalia;Peinelt, Christine
存储操作钙离子（2+）进入是存在于大多数细胞类型中的主要钙离子（2+）进入机制。在免疫细胞中，储存操作的Ca（2+）进入几乎完全由Ca（2+）释放激活的Ca(2+) （CRAC）通道介导。钙（2+）通过这些通道进入细胞以及相应的胞质钙（2+）信号是许多免疫细胞功能所必需的，包括t细胞活化的各个方面。ORAI蛋白是CRAC通道的分子相关物。ORAI1、ORAI2和ORAI3这三个人类成员在内质网Ca（2+）储存耗尽后，通过基质相互作用分子（STIM）1和2被激活。不同的STIM和ORAI组合可以形成不同的CRAC通道，具有不同的生物物理性质。在这篇文章中，我们回顾并讨论了两种重要的CRAC/ORAI抑制剂，2-APB和BTP2，以及已经报道的干扰ORAI通道功能的抗生素G418的机制和功能意义。使用药理学工具应该有助于为不同的STIM-ORAI蛋白复合物分配不同的生理和病理生理功能。
Store-operated Ca(2+) entry is a major Ca(2+) entry mechanism that is present in most cell types. In immune cells, store-operated Ca(2+) entry is almost exclusively mediated by Ca(2+) release-activated Ca(2+) (CRAC) channels. Ca(2+) entry through these channels and the corresponding cytosolic Ca(2+) signals are required for many immune cell functions, including all aspects of T-cell activation. ORAI proteins are the molecular correlates for the CRAC channels. The three human members, ORAI1, ORAI2 and ORAI3, are activated through the stromal interaction molecules (STIM)1 and 2 following depletion of endoplasmic reticulum Ca(2+) stores. Different combinations of STIM and ORAI can form different CRAC channels with distinct biophysical properties. In this article, we review and discuss mechanistic and functional implications of two important CRAC/ORAI inhibitors, 2-APB and BTP2, and the antibiotic G418 that has also been reported to interfere with ORAI channel function. The use of pharmacological tools should help to assign distinct physiological and pathophysiological functions to different STIM-ORAI protein complexes.