Habas R, Kato Y, He X
Division of Neuroscience, Children's Hospital, Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Cell. 2001 Dec 28;107(7):843-54. doi: 10.1016/s0092-8674(01)00614-6.
Wnt signaling via the Frizzled (Fz) receptor controls cell polarity and movement during development, but the molecular nature of Wnt/Fz polarity signal transduction remains poorly defined. Here we report that in human cells and during Xenopus embryogenesis, Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture. Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled (Dvl) and a novel Formin homology protein Daam1. Daam1 binds to both Dvl and Rho, and mediates Wnt-induced Dvl-Rho complex formation. Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta-catenin signaling. Our study illustrates a molecular pathway from Wnt/Fz signaling to Rho activation in cell polarity signal transduction.
通过卷曲蛋白（Fz）受体介导的Wnt信号通路在发育过程中控制细胞极性和运动，但Wnt/Fz极性信号转导的分子机制仍不清楚。我们在此报告，在人类细胞和非洲爪蟾胚胎发育过程中，Wnt/Fz信号通路激活小GTP酶Rho，它是细胞骨架结构的关键调节因子。Wnt/Fz对Rho的激活需要胞质蛋白散乱蛋白（Dvl）和一种新的formin同源蛋白Daam1。Daam1与Dvl和Rho都结合，并介导Wnt诱导的Dvl-Rho复合物形成。抑制或缺失Daam1可阻止Wnt/Fz对Rho的激活以及非洲爪蟾原肠胚形成，但不影响β-连环蛋白信号通路。我们的研究阐明了细胞极性信号转导中从Wnt/Fz信号通路到Rho激活的分子途径。
