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MBC in Press, published online ahead of print February 20, 2008
Mol. Biol. Cell 10.1091/mbc.E07-12-1269

A more recent version of this article appeared on May 1, 2008
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Submitted on December 20, 2007
Accepted on February 11, 2008

GEF-H1 Couples Nocodazole-induced Microtubule Disassembly to Cell Contractility via RhoA

Yuan-Chen Chang,*{dagger} Perihan Nalbant,*{ddagger} Jörg Birkenfeld,*{sect} Zee-Fen Chang,{dagger} and Gary M. Bokoch*

*Departments of Immunology and Cell Biology, The Scripps Research Institute, La Jolla, CA 92037; {dagger}Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei, 100 Taiwan

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.

{ddagger}Present address: Center for Medical Biotechnology, Department of Molecular Cell Biology, Faculty of Biology, University of Duisburg-Essen, Universitaetsstrasse 2, 45117 Essen, Germany. {sect}Current address: Direvo Biotech AG, Nattermannallee 1, D-50829 Köln/Cologne, Germany.

Address correspondence to: Gary M. Bokoch (bokoch{at}scripps.edu)






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