|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online 26 February 2008
doi: 10.1242/jcs.020941
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Article |
1 Department of Microbiology, University of Virginia Health System, Charlottesville, VA 22908, USA
2 Department of Neurobiology and Anatomy, West Virginia University, Morgantown, WV 26506, USA
3 Departments of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
* Author for correspondence (e-mail: jtp{at}virginia.edu)
Accepted 21 December 2007
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.
Key words: Kinase, Migration, GTPase, Adhesion
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. M. Goldyn, B. A. Rioja, J. P. Spatz, C. Ballestrem, and R. Kemkemer Force-induced cell polarisation is linked to RhoA-driven microtubule-independent focal-adhesion sliding J. Cell Sci., October 15, 2009; 122(20): 3644 - 3651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Haudek, D. Gupta, O. Dewald, R. J. Schwartz, L. Wei, J. Trial, and M. L. Entman Rho kinase-1 mediates cardiac fibrosis by regulating fibroblast precursor cell differentiation Cardiovasc Res, August 1, 2009; 83(3): 511 - 518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. N. Lyle, N. N. Deshpande, Y. Taniyama, B. Seidel-Rogol, L. Pounkova, P. Du, C. Papaharalambus, B. Lassegue, and K. K. Griendling Poldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells Circ. Res., July 31, 2009; 105(3): 249 - 259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Shi, C. G. Pontrello, K. A. DeFea, L. F. Reichardt, and I. M. Ethell Focal Adhesion Kinase Acts Downstream of EphB Receptors to Maintain Mature Dendritic Spines by Regulating Cofilin Activity J. Neurosci., June 24, 2009; 29(25): 8129 - 8142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Manso, S.-M. Kang, S. V. Plotnikov, I. Thievessen, J. Oh, H. E. Beggs, and R. S. Ross Cardiac fibroblasts require focal adhesion kinase for normal proliferation and migration Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H627 - H638. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Germain, T. M. Santos, and I. Rabinovitz Phosphorylation of a Novel Site on the {beta}4 Integrin at the Trailing Edge of Migrating Cells Promotes Hemidesmosome Disassembly Mol. Biol. Cell, January 1, 2009; 20(1): 56 - 67. [Abstract] [Full Text] [PDF]
|
|
