Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity
Rack1 is required for Vangl2 membrane localization and planar cell polarity signaling while attenuating canonical Wnt activity
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Rack1 是 Vangl2 膜定位和平面细胞极性信号传导所必需的，同时减弱经典 Wnt 活性
DOI：
10.1073/pnas.1013170108
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发表时间：
2011-02-08
影响因子：
11.1
通讯作者：
Chen, Ping
中科院分区：
文献类型：
--
作者：
Li, Shuangding;Esterberg, Robert;Chen, Ping
脊椎动物平面细胞极性 (PCP) 途径与 β-连环蛋白介导的经典 Wnt 途径共享分子成分，但通过含有 Vang 或 Frizzled 的膜复合物发挥作用，以协调定向相邻细胞。然而，Vang 在 PCP 信号传导和规范中作用的分子相互作用尚未阐明。在这里，我们报告了 Rack1 被鉴定为脊椎动物 Vang 蛋白 Vangl2 的相互作用蛋白。我们证明，Rack1 是斑马鱼 PCP 调节过程所必需的，包括定向细胞分裂、细胞极化和原肠胚形成过程中的会聚延伸。我们进一步表明，Rack1 的敲低会影响 Vangl2 的膜定位，并且 Rack1 的 Vangl2 相互作用域对 Vangl2 定位和原肠胚形成具有显性负效应。此外，Rack1 拮抗经典的 Wnt 信号传导。总之，我们的数据表明，Rack1 调节必需 PCP 蛋白的定位，并充当促进 PCP 信号传导的分子开关。
The vertebrate planar cell polarity (PCP) pathway shares molecular components with the beta-catenin-mediated canonical Wnt pathway but acts through membrane complexes containing Vang or Frizzled to orient neighboring cells coordinately. The molecular interactions underlying the action of Vang in PCP signaling and specification, however, are yet to be delineated. Here, we report the identification of Rack1 as an interacting protein of a vertebrate Vang protein, Vangl2. We demonstrate that Rack1 is required in zebrafish for PCP-regulated processes, including oriented cell division, cellular polarization, and convergent extension during gastrulation. We further show that the knockdown of Rack1 affects membrane localization of Vangl2 and that the Vangl2-interacting domain of Rack1 has a dominant-negative effect on Vangl2 localization and gastrulation. Moreover, Rack1 antagonizes canonical Wnt signaling. Together, our data suggest that Rack1 regulates the localization of an essential PCP protein and acts as a molecular switch to promote PCP signaling.