Kida Yasuyuki S, Sato Takayuki, Miyasaka Kota Y, Suto Asami, Ogura Toshihiko
Department of Developmental Neurobiology, Institute of Development, Aging, and Cancer, Tohoku University, 4-1, Seiryo, Aoba, Sendai, Miyagi 980-8575, Japan.
Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6708-13. doi: 10.1073/pnas.0608946104. Epub 2007 Apr 5.
Convergent extension (CE) movement of cells is one of the fundamental processes that control the organized morphogenesis of tissues and organs. The molecular events connecting the noncanonical Wnt pathway and CE movement, however, are not well understood. We show that subcellular localization of Daam1, an essential component of noncanonical Wnt signaling, changes dynamically during notochord formation. In the early phases, Daam1 complexes with EphB receptors and Disheveled 2. This complex is incorporated into endocytic vesicles in a dynamin-dependent manner, thereby resulting in the removal of EphB from the cell surface with subsequent switching of cell adhesiveness. In the next step, Daam1 colocalizes with the actin cytoskeleton to induce morphological extension of cells. We elucidate the molecular mechanism underlying the CE movement of notochord cells with Daam1 as a dynamic coordinator of endocytosis and cytoskeletal remodeling.
细胞的汇聚延伸（CE）运动是控制组织和器官有序形态发生的基本过程之一。然而，连接非经典Wnt信号通路与CE运动的分子事件尚未得到充分理解。我们发现，非经典Wnt信号的重要组成部分Daam1的亚细胞定位在脊索形成过程中动态变化。在早期阶段，Daam1与EphB受体和Disheveled 2形成复合物。该复合物以发动蛋白依赖的方式被纳入内吞小泡，从而导致EphB从细胞表面移除，随后细胞黏附性发生改变。在下一步中，Daam1与肌动蛋白细胞骨架共定位，以诱导细胞的形态延伸。我们阐明了以Daam1作为内吞作用和细胞骨架重塑的动态协调者的脊索细胞CE运动的分子机制。
