Transient receptor potential ankyrin-1 (TRPA1) modulates store-operated Ca2+ entry by regulation of STIM1-Orai1 association
Transient receptor potential ankyrin-1 (TRPA1) modulates store-operated Ca2+ entry by regulation of STIM1-Orai1 association
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DOI：
10.1016/j.bbamcr.2013.08.014
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发表时间：
2013-12-01
影响因子：
5.1
通讯作者：
Rosado, Juan A.
中科院分区：
文献类型：
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作者：
Albarran, Letizia;Lopez, Jose J.;Rosado, Juan A.
TRPA1 是位于质膜中的非选择性 Ca2+ 渗透通道，作为检测机械、化学和热刺激的细胞传感器，是神经元、上皮、血液和平滑肌组织的组成部分。 TRPA1 已被证明可以影响涉及 Ca2+ 依赖性信号通路的广泛生理过程。在这里，我们报道TRPA1在蛋白质水平上在MEGO1中表达，但在血小板中不表达。 PMA 诱导的 MEGO1 细胞成熟导致 TRPA1 蛋白表达减弱，并增强毒胡萝卜素诱发的 Ca2+ 进入，而不改变细胞内储存的 Ca2+ 释放。 HC-030031 抑制 TRPA1 会增强凝血酶和毒胡萝卜素刺激的 Ca2+ 进入。免疫共沉淀实验表明，TRPA1 与 STIM1、Orai1、TRPC1 和 TRPC6 相关。 MEGO1 成熟导致 TRPA1 表达下调，以及 HC-030031 对 TRPA1 的药理学抑制，导致 STIM1 和 Orai1 之间的关联增强。总而言之，这些发现为 TRPA1 在细胞功能中的新的有趣功能提供了证据，该功能与通过调节 STIM1/Orai1 相互作用来调节激动剂诱导的 Ca2+ 进入相关。 (C) 2013 Elsevier B.V. 保留所有权利。
TRPA1 is a non-selective Ca2+ permeable channel located in the plasma membrane that functions as a cellular sensor detecting mechanical, chemical and thermal stimuli, being a component of neuronal, epithelial, blood and smooth muscle tissues. TRPA1 has been shown to influence a broad range of physiological processes that involve Ca2+-dependent signaling pathways. Here we report that TRPA1 is expressed in MEGO1 but not in platelets at the protein level. MEGO1 cells maturation induced by PMA results in attenuation of TRPA1 protein expression and enhances thapsigargin-evoked Ca2+ entry without altering the release of Ca2+ from intracellular stores. Inhibition of TRPA1 by HC-030031 results in enhancement of both thrombin- and thapsigargin-stimulated Ca2+ entry. Co-immunoprecipitation experiments revealed that TRPA1 associates with STIM1, as well as Orai1, TRPC1 and TRPC6. Downregulation of TRPA1 expression by MEGO1 maturation, as well as pharmacological inhibition of TRPA1 by HC-030031, results in enhancement of the association between STIM1 and Orai1. Altogether, these findings provide evidence for a new and interesting function of TRPA1 in cellular function associated to the regulation of agonist-induced Ca2+ entry by the modulation of STIM1/Orai1 interaction. (C) 2013 Elsevier B.V. All rights reserved.