Zihni Ceniz, Vlassaks Evi, Terry Stephen, Carlton Jeremy, Leung Thomas King Chor, Olson Michael, Pichaud Franck, Balda Maria Susana, Matter Karl
Institute of Ophthalmology, University College London, Bath Street, London EC1V 9EL, UK.
MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
Nat Cell Biol. 2017 Sep;19(9):1049-1060. doi: 10.1038/ncb3592. Epub 2017 Aug 21.
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.
极化上皮细胞形成不同的细胞表面结构域，顶端膜具有微绒毛等特征性形态特征。细胞极化由极性决定因子驱动，包括进化上保守的分区缺陷（PAR）蛋白，这些蛋白被分隔到不同的皮质结构域。PAR蛋白的分离被认为是肌动球蛋白不对称收缩的结果。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，我们表明Cdc42效应器MRCK在顶端极激活肌球蛋白-II，将aPKC-Par6与连接蛋白Par3分离，从而定义顶端结构域。顶端极化的MRCK激活的肌动球蛋白收缩性通过与aPKC-Par6协同作用而增强，aPKC-Par6下调拮抗的RhoA驱动的连接肌动球蛋白收缩性，并驱动细胞质刷状缘决定因子的极化和顶端形态发生。MRCK激活的极化肌动球蛋白收缩性是脊椎动物上皮细胞和果蝇光感受器顶端分化和形态发生所必需的。我们的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极性信号联系起来。
