daam1 is a formin required for centrosome re-orientation during cell migration中心体所需daam1是甲酸精定位在细胞迁移.pdf

DAAM1 Is a Formin Required for Centrosome Re- Orientation during Cell Migration 3 1 2 1,3 Su-Fen Ang , Zhuo-shen Zhao , Louis Lim , Ed Manser * 1 small G-protein Signaling and Kinases-Neuroscience Research Partnership (sGSK-NRP) Group, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore, 2 Institute of Neurology, University College London, London, United Kingdom, 3 Rho GTPases in Stem Cells (RGS) Group, Institute of Medical Biology Agency for Science, Technology and Research (A*STAR), Singapore, Singapore Abstract Background: Disheveled-associated activator of morphogenesis 1 (DAAM1) is a formin acting downstream of Wnt signaling that is important for planar cell polarity. It has been shown to promote proper cell polarization during embryonic development in both Xenopus and Drosophila. Importantly, DAAM1 binds to Disheveled (Dvl) and thus functions downstream of the Frizzled receptors. Little is known of how DAAM1 is localized and functions in mammalian cells. We investigate here how DAAM1 affects migration and polarization of cultured cells and conclude that it plays a key role in centrosome polarity. Methodology/Principal Findings: Using a specific antibody to DAAM1, we find that the protein localizes to the acto-myosin system and co-localizes with ventral myosin IIB-containing actin stress fibers. These fibers are particularly evident in the sub- nuclear region. An N-terminal region of DAAM1 is responsible for this targeting and the DAAM1(1-440) protein can interact with myosin IIB fibers independently of either F-actin or RhoA binding. We also demonstrate that DAAM1 depletion inhibits Golgi reorientation in wound healing assays. Wound-edge cells exhibit mult