Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton
Nucleotide exchange factor GEF-H1 mediates cross-talk between microtubules and the actin cytoskeleton
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DOI：
10.1038/ncb773
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发表时间：
2002-04-01
影响因子：
21.3
通讯作者：
Bokoch, GM
中科院分区：
文献类型：
--
作者：
Krendel, M;Zenke, FT;Bokoch, GM
微管对肌动蛋白细胞骨架的调节是由Rho家族GTP酶介导的。然而，将微管动力学与Rho GTP酶联系起来的分子机制尚未确定。在这里，我们证明了Rho鸟嘌呤核苷酸交换因子(Global)-H1是由与微管的相互作用调节的。缺乏微管结合的突变体具有比微管结合形式更高的活性水平。这些突变体还诱导细胞形态和肌动蛋白组织发生依赖于Rho的变化。此外，药物诱导的微管解聚导致细胞形态和基因表达的变化，这与活性形式的全球环境基金-H1的表达所引起的变化相似。此外，这些效应被显性-负性版本的全球环境基金-H1抑制。因此，全球环境基金-H1将微管完整性的变化与Rho依赖的肌动蛋白细胞骨架的调节联系起来。
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.