Kim Gun-Hwa, Her Jung-Hyun, Han Jin-Kwan
Department of Life Science, Division of Molecular and Life Sciences, Pohang University of Science and Technology, Hyoja Dong, Pohang, Kyungbuk 790-784, Republic of Korea.
J Cell Biol. 2008 Sep 22;182(6):1073-82. doi: 10.1083/jcb.200710188.
The single-pass transmembrane protein Ryk (atypical receptor related tyrosine kinase) functions as a Wnt receptor. However, Ryk's correlation with Wnt/Frizzled (Fz) signaling is poorly understood. Here, we report that Ryk regulates Xenopus laevis convergent extension (CE) movements via the beta-arrestin 2 (betaarr2)-dependent endocytic process triggered by noncanonical Wnt signaling. During X. laevis gastrulation, betaarr2-mediated endocytosis of Fz7 and dishevelled (Dvl/Dsh) actually occurs in the dorsal marginal zone tissues, which actively participate in noncanonical Wnt signaling. Noncanonical Wnt11/Fz7-mediated endocytosis of Dsh requires the cell-membrane protein Ryk. Ryk interacts with both Wnt11 and betaarr2, cooperates with Fz7 to mediate Wnt11-stimulated endocytosis of Dsh, and signals the noncanonical Wnt pathway in CE movements. Conversely, depletion of Ryk and Wnt11 prevents Dsh endocytosis in dorsal marginal zone tissues. Our study suggests that Ryk functions as an essential regulator for noncanonical Wnt/Fz-mediated endocytosis in the regulation of X. laevis CE movements.
单次跨膜蛋白Ryk（非典型受体相关酪氨酸激酶）作为一种Wnt受体发挥作用。然而，Ryk与Wnt/卷曲蛋白（Fz）信号传导之间的关联仍知之甚少。在此，我们报告Ryk通过由非经典Wnt信号触发的β-抑制蛋白2（βarr2）依赖性内吞过程来调节非洲爪蟾的汇聚延伸（CE）运动。在非洲爪蟾原肠胚形成过程中，βarr2介导的Fz7和散乱蛋白（Dvl/Dsh）的内吞作用实际上发生在背侧边缘区组织中，这些组织积极参与非经典Wnt信号传导。非经典Wnt11/Fz7介导的Dsh内吞作用需要细胞膜蛋白Ryk。Ryk与Wnt11和βarr2都相互作用，与Fz7协同介导Wnt11刺激的Dsh内吞作用，并在CE运动中传导非经典Wnt信号通路。相反，Ryk和Wnt11的缺失会阻止背侧边缘区组织中Dsh的内吞作用。我们的研究表明，在调节非洲爪蟾CE运动中，Ryk作为非经典Wnt/Fz介导的内吞作用的关键调节因子发挥作用。
