Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling
Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling
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DOI：
10.1242/dev.019646
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发表时间：
2008-04-15
期刊：
影响因子：
4.6
通讯作者：
Takeichi, Masatoshi
中科院分区：
文献类型：
--
作者：
Nishimura, Tamako;Takeichi, Masatoshi
上皮细胞的重塑在动物形态发生中起着重要的作用。Shroom3调节上皮细胞的顶端收缩。在这里，我们发现Shroom3结合岩石并将它们招募到上皮顶端连接处。我们在岩石上鉴定了Shroom3-结合位点（RII-C1），发现RII-C1可以拮抗Shroom3- ROCK相互作用，干扰Shroom3对细胞形态的作用。在内陷神经板/管中，Shroom3与岩石在根尖连接处定位；Shroom3缺失或RII-C1在管中表达可使这些顶端定位的岩石消失，并同时阻断神经管闭合。闭合神经板表现出特殊的细胞组合，包括玫瑰结形成，以及磷酸化的肌球蛋白调节轻链的平面极化分布，但这些都被ROCK抑制或RII-C1表达所消除。这些结果表明，Shroom3- ROCK相互作用对上皮和神经上皮细胞的排列和重塑的调节至关重要。
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.