Regulation of cell-matrix adhesion by OLA1, the Obg-like ATPase 1.
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.
Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX 77030, USA.
Prince V S
PV
Jeyabal
Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX 77030, USA.
Valentina
V
Rubio
Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX 77030, USA.
Huarong
H
Chen
Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX 77030, USA.
Jiawei
J
Zhang
Department of Translational Imaging, Houston Methodist Research Institute, Houston, TX 77030, USA. Electronic address: zshi@HoustonMethodist.org.
Zheng-Zheng
ZZ
Shi
D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D034622:RNA Interference; D015854:Up-Regulation
D051339:Actin Depolymerizing Factors; D051416:Focal Adhesion Protein-Tyrosine Kinases; D000251:Adenosine Triphosphatases; D019204:GTP-Binding Proteins; C522732:OLA1 protein, human
Cell spreading; Cell-matrix adhesion; Cofilin; FAK; OLA1