Polarized epithelia develop distinct cell surface domains, with the apical membrane acquiring characteristic morphological features such as microvilli. Cell polarization is driven by polarity determinants including the evolutionarily conserved partitioning-defective (PAR) proteins that are separated into distinct cortical domains. PAR protein segregation is thought to be a consequence of asymmetric actomyosin contractions. The mechanism of activation of apically polarized actomyosin contractility is unknown. Here we show that the Cdc42 effector MRCK activates myosin-II at the apical pole to segregate aPKC-Par6 from junctional Par3, defining the apical domain. Apically polarized MRCK-activated actomyosin contractility is reinforced by cooperation with aPKC-Par6 downregulating antagonistic RhoA-driven junctional actomyosin contractility, and drives polarization of cytosolic brush border determinants and apical morphogenesis. MRCK-activated polarized actomyosin contractility is required for apical differentiation and morphogenesis in vertebrate epithelia and Drosophila photoreceptors. Our results identify an apical origin of actomyosin-driven morphogenesis that couples cytoskeletal reorganization to PAR polarity signalling.

中文翻译：

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顶端 MRCK 驱动的形态发生通路控制上皮极性。

极化上皮形成不同的细胞表面结构域，顶端膜获得特征性的形态特征，如微绒毛。细胞极化是由极性决定因素驱动的，包括进化上保守的分区缺陷 (PAR) 蛋白，这些蛋白被分成不同的皮层结构域。PAR 蛋白分离被认为是不对称肌动球蛋白收缩的结果。顶端极化的肌动球蛋白收缩性的激活机制尚不清楚。在这里，我们显示 Cdc42 效应器 MRCK 在顶端激活肌球蛋白-II，以将 aPKC-Par6 与连接 Par3 分离，定义顶端域。顶端极化的 MRCK 激活的肌动球蛋白收缩性通过与 aPKC-Par6 下调拮抗性 RhoA 驱动的连接肌动球蛋白收缩性的合作得到加强，并驱动细胞溶质刷状缘决定因素和顶端形态发生的极化。脊椎动物上皮细胞和果蝇光感受器的顶端分化和形态发生需要 MRCK 激活的极化肌动球蛋白收缩性。我们的研究结果确定了肌动球蛋白驱动的形态发生的顶端起源，它将细胞骨架重组与 PAR 极性信号传导相结合。