Regulation of cell-matrix adhesion by OLA1, the Obg-like ATPase 1

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• 作者：Prince V.S. Jeyabal ; Valentina Rubio ; Huarong Chen¹ ; Jiawei Zhang¹ ; Zheng-Zheng Shi ; ^{zshi@HoustonMethodist.org" class="auth_mail}
• 关键词：OLA1 ; Obg-like ATPase 1 ; FAs ; focal adhesions ; FAK ; focal adhesion kinase ; ECM ; extracellular matrix ; ROCK ; Rho-associated kinase ; F-actin ; filamentous actin ; LIMKs ; Lim family kinases ; TESK ; testicular protein kinases ; pFAK(Y397) ; Tyr 397 phosphorylated FAK ; pFAK(Y925) ; Tyr 925 phosphorylated FAK ; pCofilin ; Ser 3 phosphorylated cofilin ; pRac/cdc42 ; Ser 71 phosphorylated Rac/cdc42 ; pVASP ; Ser 157 phosphorylated VASP
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：21 February, 2014
• 年：2014
• 卷：444
• 期：4
• 页码：568-574
• 全文大小：1497 K

文摘

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.