Article abstract
Nature Cell Biology 4, 294 - 301 (2002)
Published online: 25 March 2002 | doi:10.1038/ncb773
Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton
Mira Krendel1,3, Frank T. Zenke2,3 & Gary M. Bokoch1
Abstract
Regulation of the actin cytoskeleton by microtubules is mediated by the Rho family GTPases. However, the molecular mechanisms that link microtubule dynamics to Rho GTPases have not, as yet, been identified. Here we show that the Rho guanine nucleotide exchange factor (GEF)-H1 is regulated by an interaction with microtubules. GEF-H1 mutants that are deficient in microtubule binding have higher activity levels than microtubule–bound forms. These mutants also induce Rho-dependent changes in cell morphology and actin organization. Furthermore, drug-induced microtubule depolymerization induces changes in cell morphology and gene expression that are similar to the changes induced by the expression of active forms of GEF-H1. Furthermore, these effects are inhibited by dominant-negative versions of GEF-H1. Thus, GEF-H1 links changes in microtubule integrity to Rho-dependent regulation of the actin cytoskeleton.
- Departments of Immunology and Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA
- Present address: Merck KgaA, Department of Oncology, Preclinical R&D, Frankfurter Strasse 250, 64293 Darmstadt, Germany
- These authors contributed equally to this work.
Correspondence to: Gary M. Bokoch1 e-mail: bokoch@scripps.edu
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