Regulation of cell-matrix adhesion by OLA1, the Obg-like ATPase 1.
Regulation of cell-matrix adhesion by OLA1, the Obg-like ATPase 1.
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OLA1（Obg 样 ATPase 1）对细胞基质粘附的调节。
DOI：
10.1016/j.bbrc.2014.01.099
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发表时间：
2014-02-21
影响因子：
3.1
通讯作者：
Shi, Zheng-Zheng
中科院分区：
文献类型：
--
作者：
Jeyabal, Prince V. S.;Rubio, Valentina;Chen, Huarong;Zhang, Jiawei;Shi, Zheng-Zheng
细胞与细胞外基质的附着诱导膜受体整合素聚集，进而引发局灶黏附（FAs）的形成。FAs中的接头/支架蛋白提供与肌动蛋白细胞骨架的连接，而局灶黏附激酶（FAK）和其他fa相关的激酶和磷酸酶转导整合素介导的信号级联，促进肌动蛋白聚合和细胞扩散的进展。在这项研究中，我们探索了OLA1在调节细胞粘附过程中的作用，OLA1是obg样atp酶的新成员。我们发现，在多种人类细胞系中，rnai介导的OLA1下调显著加速了细胞的粘附和扩散，相反，通过基因转染过表达OLA1导致细胞的粘附和扩散延迟。我们进一步发现，ola1缺失的细胞FAK蛋白水平升高，cofilin（肌动蛋白结合蛋白和肌动蛋白丝动力学的关键调节因子）的Ser3磷酸化水平降低，而ola1过表达的细胞FAK和cofilin的分子变化相反。这些研究结果表明，OLA1在细胞粘附和扩散中起着重要的负作用，部分通过调节FAK表达和cofilin磷酸化，并且操纵OLA1可能导致细胞粘附和相关表型的显着变化。
Attachment of cells to the extracellular matrix induces clustering of membrane receptor integrins which in turn triggers the formation of focal adhesions (FAs). The adaptor/scaffold proteins in FAs provide linkage to actin cytoskeleton, whereas focal adhesion kinase (FAK) and other FA-associated kinases and phosphatases transduce integrin-mediated signaling cascades, promoting actin polymerization and progression of cell spreading. In this study, we explored the role of OLA1, a newly identified member of Obg-like ATPases, in regulating cell adhesion processes. We showed that in multiple human cell lines RNAi-mediated downregulation of OLA1 significantly accelerated cell adhesion and spreading, and conversely overexpression of OLA1 by gene transfection resulted in delayed cell adhesion and spreading. We further found that OLA1-deficient cells had elevated levels of FAK protein and decreased Ser3 phosphorylation of cofilin, an actin-binding protein and key regulator of actin filament dynamics, while OLA1-overexpressing cells exhibited the opposite molecular alterations in FAK and cofilin. These findings suggest that OLA1 plays an important negative role in cell adhesion and spreading, in part through the regulation of FAK expression and cofilin phosphorylation, and manipulation of OLA1 may lead to significant changes in cell adhesion and the associated phenotypes.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
4
作者：
Daley, William P.;Yamada, Kenneth M.
通讯作者：
Yamada, Kenneth M.
影响因子：
7.7
作者：
Simpson, JC;Wellenreuther, R;Wiemann, S
通讯作者：
Wiemann, S
DOI：
10.1083/jcb.200708194
发表时间：
2008-01-14
期刊：
The Journal of cell biology
影响因子：
--
作者：
Lim Y;Lim ST;Tomar A;Gardel M;Bernard-Trifilo JA;Chen XL;Uryu SA;Canete-Soler R;Zhai J;Lin H;Schlaepfer WW;Nalbant P;Bokoch G;Ilic D;Waterman-Storer C;Schlaepfer DD
通讯作者：
Schlaepfer DD
影响因子：
4
作者：
Gradia, Daniela F.;Rau, Karlan;Fragoso, Stenio P.
通讯作者：
Fragoso, Stenio P.