![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 19, Issue 5, 2147-2153, May 2008
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; and Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100 Taiwan
Submitted December 20, 2007;
Accepted February 11, 2008
Monitoring Editor: Paul Forscher
The RhoA GTPase plays a vital role in assembly of contractile actin-myosin filaments (stress fibers) and of associated focal adhesion complexes of adherent monolayer cells in culture. GEF-H1 is a microtubule-associated guanine nucleotide exchange factor that activates RhoA upon release from microtubules. The overexpression of GEF-H1 deficient in microtubule binding or treatment of HeLa cells with nocodazole to induce microtubule depolymerization results in Rho-dependent actin stress fiber formation and contractile cell morphology. However, whether GEF-H1 is required and sufficient to mediate nocodazole-induced contractility remains unclear. We establish here that siRNA-mediated depletion of GEF-H1 in HeLa cells prevents nocodazole-induced cell contraction. Furthermore, the nocodazole-induced activation of RhoA and Rho-associated kinase (ROCK) that mediates phosphorylation of myosin regulatory light chain (MLC) is impaired in GEF-H1–depleted cells. Conversely, RhoA activation and contractility are rescued by reintroduction of siRNA-resistant GEF-H1. Our studies reveal a critical role for a GEF-H1/RhoA/ROCK/MLC signaling pathway in mediating nocodazole-induced cell contractility.
Present addresses: 
Center for Medical Biotechnology, Department of Molecular Cell Biology, Faculty of Biology, University of Duisburg-Essen, Universitätsstraße 2, 45117 Essen, Germany;
Direvo Biotech AG, Nattermannallee 1, D-50829 Köln, Germany.
Address correspondence to: Gary M. Bokoch (bokoch{at}scripps.edu)
This article has been cited by other articles:
|
|
 |
|
  Y. Cai, O. Rossier, N. C. Gauthier, N. Biais, M.-A. Fardin, X. Zhang, L. W. Miller, B. Ladoux, V. W. Cornish, and M. P. Sheetz Cytoskeletal coherence requires myosin-IIA contractility J. Cell Sci., February 1, 2010; 123(3): 413 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. K. Tripathi and P. S. Zelenka Cdk5-Dependent Regulation of Rho Activity, Cytoskeletal Contraction, and Epithelial Cell Migration via Suppression of Src and p190RhoGAP Mol. Cell. Biol., December 15, 2009; 29(24): 6488 - 6499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Nalbant, Y.-C. Chang, J. Birkenfeld, Z.-F. Chang, and G. M. Bokoch Guanine Nucleotide Exchange Factor-H1 Regulates Cell Migration via Localized Activation of RhoA at the Leading Edge Mol. Biol. Cell, September 15, 2009; 20(18): 4070 - 4082. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Kakiashvili, P. Speight, F. Waheed, R. Seth, M. Lodyga, S. Tanimura, M. Kohno, O. D. Rotstein, A. Kapus, and K. Szaszi GEF-H1 Mediates Tumor Necrosis Factor-{alpha}-induced Rho Activation and Myosin Phosphorylation: ROLE IN THE REGULATION OF TUBULAR PARACELLULAR PERMEABILITY J. Biol. Chem., April 24, 2009; 284(17): 11454 - 11466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Samarin, M. Rehm, B. Krueger, J. Waschke, and M. Goppelt-Struebe Up-Regulation of Connective Tissue Growth Factor in Endothelial Cells by the Microtubule-Destabilizing Agent Combretastatin A-4 Mol. Cancer Res., February 1, 2009; 7(2): 180 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. G. Young, S. F. Thurston, S. Copeland, C. Smallwood, and J. W. Copeland INF1 Is a Novel Microtubule-associated Formin Mol. Biol. Cell, December 1, 2008; 19(12): 5168 - 5180. [Abstract] [Full Text] [PDF]
|
|
