Actin realignment and cofilin regulation are essential for barrier integrity during shear stress.
Actin realignment and cofilin regulation are essential for barrier integrity during shear stress.
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DOI：
10.1002/jcb.24416
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发表时间：
2013-04
影响因子：
4
通讯作者：
Lowe-Krentz, Linda J.
中科院分区：
文献类型：
--
作者：
Slee, Joshua B.;Lowe-Krentz, Linda J.
体外和体内血管内皮细胞及其肌动蛋白微丝沿流体剪切应力（FSS）方向排列。为了确定在这一过程中是否需要肌动蛋白切断蛋白cofilin，我们在暴露于FSS的细胞中评估了phospho-cofilin（丝氨酸-3）的水平。在FSS暴露期间，细胞质中的磷酸化-cofilin水平降低，细胞核中的磷酸化-cofilin水平升高。这伴随着活化的LIMK（一种cofilin激酶）的核染色增加。阻断应激激酶JNK和p38，已知在FSS期间参与肌动蛋白重组，在静态条件下降低cofilin磷酸化，JNK抑制也导致FSS暴露期间磷酸化-cofilin减少。通过cofilin突变体抑制cofilin磷酸化的动态变化减少了正确的肌动蛋白重组。突变体也降低了屏障的完整性，就像抑制应激激酶一样。这些结果确定了cofilin在肌动蛋白排列过程中的重要性，以及FSS过程中肌动蛋白重新排列对内皮屏障完整性的要求。
Vascular endothelial cells and their actin microfilaments align in the direction of fluid shear stress (FSS) in vitro and in vivo. To determine whether cofilin, an actin severing protein, is required in this process, the levels of phospho-cofilin (serine-3) were evaluated in cells exposed to FSS. Phospho-cofilin levels decreased in the cytoplasm and increased in the nucleus during FSS exposure. This was accompanied by increased nuclear staining for activated LIMK, a cofilin kinase. Blocking stress kinases JNK and p38, known to play roles in actin realignment during FSS, decreased cofilin phosphorylation under static conditions, and JNK inhibition also resulted in decreased phospho-cofilin during FSS exposure. Inhibition of dynamic changes in cofilin phosphorylation through cofilin mutants decreased correct actin realignment. The mutants also decreased barrier integrity as did inhibition of the stress kinases. These results identify the importance of cofilin in the process of actin alignment and the requirement for actin realignment in endothelial barrier integrity during FSS.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
影响因子：
15.9
作者：
Li, S;Chen, BPC;Chien, S
通讯作者：
Chien, S
DOI：
10.1083/jcb.200401136
发表时间：
2004-05-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Nagata-Ohashi K;Ohta Y;Goto K;Chiba S;Mori R;Nishita M;Ohashi K;Kousaka K;Iwamatsu A;Niwa R;Uemura T;Mizuno K
通讯作者：
Mizuno K
DOI：
10.1016/j.biocel.2006.11.011
发表时间：
2007-01-01
影响因子：
4
作者：
Bernard, Ora
通讯作者：
Bernard, Ora
影响因子：
4.8
作者：
Cote, Maxime C.;Lavoie, Jessie R.;Huot, Jacques
通讯作者：
Huot, Jacques