Nishimura Tamako, Takeichi Masatoshi
RIKEN Center for Developmental Biology, 2-2-3 Minatojima-Minamimachi, Chuo-ku, Kobe 650-0047, Japan.
Development. 2008 Apr;135(8):1493-502. doi: 10.1242/dev.019646. Epub 2008 Mar 13.
Remodeling of epithelial sheets plays important roles in animal morphogenesis. Shroom3 is known to regulate the apical constriction of epithelial cells. Here, we show that Shroom3 binds ROCKs and recruits them to the epithelial apical junctions. We identified the Shroom3-binding site (RII-C1) on ROCKs, and found that RII-C1 could antagonize the Shroom3-ROCK interaction, interfering with the action of Shroom3 on cell morphology. In the invaginating neural plate/tube, Shroom3 colocalized with ROCKs at the apical junctions; Shroom3 depletion or RII-C1 expression in the tube removed these apically localized ROCKs, and concomitantly blocked neural tube closure. Closing neural plate exhibited peculiar cell assemblies, including rosette formation, as well as a planar-polarized distribution of phosphorylated myosin regulatory light chain, but these were abolished by ROCK inhibition or RII-C1 expression. These results demonstrate that the Shroom3-ROCK interaction is crucial for the regulation of epithelial and neuroepithelial cell arrangement and remodeling.
上皮细胞层的重塑在动物形态发生过程中发挥着重要作用。已知Shroom3可调节上皮细胞的顶端收缩。在此，我们表明Shroom3与ROCKs结合并将它们募集到上皮顶端连接处。我们鉴定出了ROCKs上的Shroom3结合位点（RII-C1），并发现RII-C1可拮抗Shroom3与ROCK的相互作用，干扰Shroom3对细胞形态的作用。在向内凹陷的神经板/神经管中，Shroom3与ROCKs在上皮顶端连接处共定位；在神经管中Shroom3缺失或RII-C1表达会去除这些位于顶端的ROCKs，并同时阻止神经管闭合。正在闭合的神经板表现出特殊的细胞聚集，包括玫瑰花结的形成，以及磷酸化肌球蛋白调节轻链的平面极化分布，但这些现象会被ROCK抑制或RII-C1表达所消除。这些结果表明，Shroom3与ROCK的相互作用对于调节上皮和神经上皮细胞的排列及重塑至关重要。
