FAK, PDZ-RhoGEF and ROCKII cooperate to regulate adhesion movement and trailing-edge retraction in fibroblasts
Open Access
- 15 March 2008
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 121 (6), 895-905
- https://doi.org/10.1242/jcs.020941
Abstract
A key step in cell migration is the dynamic formation and disassembly of adhesions at the front and the concomitant movement and release of adhesions in the rear of the cell. Fibroblasts maintained in the absence of serum have stable adhesions within the rear of the cell and exhibit reduced trailing-edge retraction resulting in an elongated cell phenotype. Addition of lysophosphatidic acid (LPA) induced the movement of adhesions and retraction of the trailing edge, thus mimicking tail retraction in a migrating cell. Focal adhesion kinase (FAK), guanine nucleotide exchange factors (GEF) for Rho and the Rho effector Rho kinase II (ROCKII) are crucial for the regulation of adhesion movement and trailing-edge retraction. Downregulation of FAK by small interfering RNAs or small hairpin RNAs blocked LPA-induced adhesion movement and restoration of cell shape. This phenotype was rescued by the ectopic expression of PDZ-RhoGEF or a RhoA-effector-domain mutant that activates ROCK. Knockdown of PDZ-RhoGEF or ROCKII inhibited LPA-induced trailing-edge retraction and adhesion movement. Moreover, overexpressed PDZ-RhoGEF co-immunoprecipitated with FAK and localized to FAK-containing adhesions. These studies support a model in which FAK and PDZ-RhoGEF cooperate to induce Rho/ROCKII-dependent focal adhesion movement and trailing-edge retraction in response to LPA.Keywords
This publication has 36 references indexed in Scilit:
- Spatial and Temporal Regulation of Focal Adhesion Kinase Activity in Living CellsMolecular and Cellular Biology, 2008
- The G12/13-RhoA signaling pathway contributes to efficient lysophosphatidic acid-stimulated cell migrationOncogene, 2005
- Identification of a Novel Sequence in PDZ-RhoGEF That Mediates Interaction with the Actin CytoskeletonMolecular Biology of the Cell, 2004
- Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potentialOncogene, 2004
- Regulation of G Protein-linked Guanine Nucleotide Exchange Factors for Rho, PDZ-RhoGEF, and LARG by Tyrosine PhosphorylationOnline Journal of Public Health Informatics, 2002
- A Novel PDZ Domain Containing Guanine Nucleotide Exchange Factor Links Heterotrimeric G Proteins to RhoOnline Journal of Public Health Informatics, 1999
- The G-protein G13 but Not G12 Mediates Signaling from Lysophosphatidic Acid Receptor via Epidermal Growth Factor Receptor to RhoOnline Journal of Public Health Informatics, 1998
- Reconstitution of Receptors and GTP-binding Regulatory Proteins (G Proteins) in Sf9 CellsOnline Journal of Public Health Informatics, 1997
- An SH3 Domain-Containing GTPase-Activating Protein for Rho and Cdc42 Associates with Focal Adhesion KinaseMolecular and Cellular Biology, 1996
- Identification of sequences required for the efficient localization of the focal adhesion kinase, pp125FAK, to cellular focal adhesions.The Journal of cell biology, 1993