STIM2 drives Ca2+ oscillations through store‐operated Ca2+ entry caused by mild store depletion
STIM2 drives Ca2+ oscillations through store‐operated Ca2+ entry caused by mild store depletion
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STIM2 通过由轻度储存耗尽引起的储存操作的 Ca2 进入来驱动 Ca2 振荡
DOI：
10.1113/jphysiol.2012.245399
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Penner R
中科院分区：
文献类型：
--
作者：
Thiel M;Penner R
基质细胞相互作用分子（STIM） 2在内质网中感知Ca2+水平，并在储存耗尽时激活质膜中的Ca2+通道。在这里，我们报告STIM2优先被低激动剂浓度激活，导致内质网Ca2+水平轻度降低。这表明存储操作Ca2+进入是通过信号强度调节的，弱刺激激活STIM2，强刺激参与STIM1。结果帮助我们了解受体激活如何使Ca2+进入的差异调节在一系列激动剂浓度和存储损耗水平。在许多细胞类型中，激动剂诱导的Ca2+振荡是由细胞内存储的Ca2+释放触发的，并由存储操作的Ca2+进入驱动。基质细胞相互作用分子（STIM） 1和STIM2作为内质网Ca2+传感器，当储存耗尽时，激活Ca2+释放激活的质膜Ca2+通道（Orai1-3, CRACM1-3）。然而，它们在激动剂介导的Ca2+振荡中的相对作用仍然不明确。在这里，我们报告说，虽然STIM1和STIM2在肥大细胞（RBL）、T细胞（Jurkat）和人胚胎肾（HEK293）细胞的Ca2+振荡期间都有助于储存-再填充，但它们依赖于储存耗尽的水平。通过siRNA或G418抑制STIM2的分子沉默，可以在低水平的存储耗尽下抑制存储操作的Ca2+进入和激动剂介导的Ca2+振荡，而不会干扰完全存储耗尽诱导的STIM1介导的信号。因此，STIM2优先被低水平的生理激动剂浓度激活，引起内质网Ca2+水平的轻度降低。我们得出的结论是，随着激动剂浓度的增加，储存操作的Ca2+进入最初由内源性STIM2介导，并逐渐由STIM1介导，从而在一系列激动剂浓度和储存消耗水平上实现Ca2+进入的差异调节。
Key pointsStromal cell‐interaction molecule (STIM) 2 senses Ca2+levels in the endoplasmic reticulum and activates Ca2+channels in the plasma membrane upon store depletion.Here we report that STIM2 is preferentially activated by low agonist concentrations that cause mild reductions in endoplasmic reticulum Ca2+levels.This shows that store‐operated Ca2+entry is regulated through signal strength, with weak stimuli activating STIM2 and strong stimuli engaging STIM1.The results help us to understand how receptor activation enables differential modulation of Ca2+entry over a range of agonist concentrations and levels of store depletion.AbstractAgonist‐induced Ca2+oscillations in many cell types are triggered by Ca2+release from intracellular stores and driven by store‐operated Ca2+entry. Stromal cell‐interaction molecule (STIM) 1 and STIM2 serve as endoplasmic reticulum Ca2+sensors that, upon store depletion, activate Ca2+release‐activated Ca2+channels (Orai1–3, CRACM1–3) in the plasma membrane. However, their relative roles in agonist‐mediated Ca2+oscillations remain ambiguous. Here we report that while both STIM1 and STIM2 contribute to store‐refilling during Ca2+oscillations in mast cells (RBL), T cells (Jurkat) and human embryonic kidney (HEK293) cells, they do so dependent on the level of store depletion. Molecular silencing of STIM2 by siRNA or inhibition by G418 suppresses store‐operated Ca2+entry and agonist‐mediated Ca2+oscillations at low levels of store depletion, without interfering with STIM1‐mediated signals induced by full store depletion. Thus, STIM2 is preferentially activated by low‐level physiological agonist concentrations that cause mild reductions in endoplasmic reticulum Ca2+levels. We conclude that with increasing agonist concentrations, store‐operated Ca2+entry is mediated initially by endogenous STIM2 and incrementally by STIM1, enabling differential modulation of Ca2+entry over a range of agonist concentrations and levels of store depletion.
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教员意见推荐 STIM1 是一种 Ca2 传感器，可激活 CRAC 通道并从 Ca2 存储迁移到质膜。
DOI：
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发表时间：
2006
期刊：
影响因子：
--
作者：
B. Nilius
通讯作者：
B. Nilius
DOI：
10.1016/0005-2736(93)90253-v
发表时间：
1993-11-07
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
DORMER, RL;CAPURRO, DE;WEBB, R
通讯作者：
WEBB, R
影响因子：
32.4
作者：
Matsumoto, Masanori;Fujii, Yoko;Baba, Yoshihiro
通讯作者：
Baba, Yoshihiro
影响因子：
4
作者：
Wu, Minnie M.;Luik, Riina M.;Lewis, Richard S.
通讯作者：
Lewis, Richard S.
DOI：
--
发表时间：
2006
期刊：
--
影响因子：
--
作者：
P. Stathopulos;Guang-yao Li;M. Plevin;J. Ames;M. Ikura
通讯作者：
P. Stathopulos;Guang-yao Li;M. Plevin;J. Ames;M. Ikura