Polyunsaturated fatty acids inhibit stimulated coupling between the ER Ca(2+) sensor STIM1 and the Ca(2+) channel protein Orai1 in a process that correlates with inhibition of stimulated STIM1 oligomerization.
Polyunsaturated fatty acids inhibit stimulated coupling between the ER Ca(2+) sensor STIM1 and the Ca(2+) channel protein Orai1 in a process that correlates with inhibition of stimulated STIM1 oligomerization.
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DOI：
10.1016/j.bbalip.2014.04.006
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发表时间：
2014-08
期刊：
影响因子：
--
通讯作者：
Baird B
中科院分区：
文献类型：
--
作者：
Holowka D;Korzeniowski MK;Bryant KL;Baird B
在许多情况下，多不饱和脂肪酸（PUFAs）被发现是细胞信号传导的有效抑制剂，我们发现急性添加微摩尔PUFAs，如亚油酸，是抗原介导的fc - ri交联或SERCA泵抑制剂thapsigargin刺激肥大细胞Ca2+反应的有效抑制剂。相反，与亚油酸具有相同碳链长度的饱和脂肪酸硬脂酸不会抑制这些反应。与这种存储操作的Ca2+进入（SOCE）的抑制一致，亚油酸抑制抗原刺激的颗粒胞吐到类似的程度。使用荧光标记的质膜Ca2+通道蛋白，AcGFP-Orai1，以及标记的ER Ca2+传感器蛋白，STIM1-mRFP，我们用一种新的荧光光谱共振能量转移方法监测这些蛋白的刺激偶联，这是SOCE所必需的。我们发现亚油酸对这种刺激偶联的有效抑制说明了SOCE的抑制。此外，我们发现亚油酸诱导了一些STIM1-STIM1关联，同时抑制了STIM1- orai1偶联之前受刺激的STIM1寡聚化。我们假设亚油酸和相关PUFAs抑制STIM1- orai1偶联的机制涉及内质网膜结构的扰动，可能是通过破坏STIM1寡聚化中重要的静电相互作用。
Polyunsaturated fatty acids (PUFAs) have been found to be effective inhibitors of cell signaling in numerous contexts, and we find that acute addition of micromolar PUFAs such as linoleic acid are effective inhibitors of Ca2+ responses in mast cells stimulated by antigen-mediated crosslinking of FcεRI or by the SERCA pump inhibitor, thapsigargin. In contrast, the saturated fatty acid, stearic acid, with the same carbon chain length as linoleic acid does not inhibit these responses. Consistent with this inhibition of store-operated Ca2+ entry (SOCE), linoleic acid inhibits antigen-stimulated granule exocytosis to a similar extent. Using the fluorescently labeled plasma membrane Ca2+ channel protein, AcGFP-Orai1, together with the labeled ER Ca2+ sensor protein, STIM1-mRFP, we monitor stimulated coupling of these proteins that is essential for SOCE with a novel spectrofluorimetric resonance energy transfer method. We find effective inhibition of this stimulated coupling by linoleic acid that accounts for the inhibition of SOCE. Moreover, we find that linoleic acid induces some STIM1-STIM1 association, while inhibiting stimulated STIM1 oligomerization that precedes STIM1-Orai1 coupling. We hypothesize that linoleic acid and related PUFAs inhibit STIM1-Orai1 coupling by a mechanism that involves perturbation of ER membrane structure, possibly by disrupting electrostatic interactions important in STIM1 oligomerization.
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影响因子：
15.3
作者：
Zhang, J;Berenstein, EH;Siraganian, RP
通讯作者：
Siraganian, RP
DOI：
10.1073/pnas.1118947109
发表时间：
2012-04-10
影响因子：
11.1
作者：
Yang, Xue;Jin, Hao;Shen, Yuequan
通讯作者：
Shen, Yuequan
影响因子：
30.5
作者：
Vig, Monika;DeHaven, Wayne I.;Kinet, Jean-Pierre
通讯作者：
Kinet, Jean-Pierre
影响因子：
32.4
作者：
Saitoh, S;Arudchandran, R;Samelson, LE
通讯作者：
Samelson, LE
影响因子：
4.8
作者：
Young, RM;Zheng, XM;Baird, B
通讯作者：
Baird, B