An apical MRCK-driven morphogenetic pathway controls epithelial polarity.
An apical MRCK-driven morphogenetic pathway controls epithelial polarity.
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DOI：
10.1038/ncb3592
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发表时间：
2017-09
影响因子：
21.3
通讯作者：
Matter K
中科院分区：
文献类型：
--
作者：
Zihni C;Vlassaks E;Terry S;Carlton J;Leung TKC;Olson M;Pichaud F;Balda MS;Matter K
极化的上皮细胞形成不同的细胞表面区域，顶端膜获得特征性的形态学特征，如微绒毛。细胞极化是由极性决定因素，包括进化保守的分区缺陷（PAR）蛋白，被分为不同的皮质域。PAR蛋白分离被认为是不对称肌动球蛋白收缩的结果。激活顶端极化肌动球蛋白收缩性的机制尚不清楚。在这里，我们表明，Cdc 42效应MRCK激活肌球蛋白-II在顶端分离aPKC-Par 6从交界的Par 3，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-Par 6合作下调拮抗性RhoA驱动的连接肌动球蛋白收缩性而得到加强，并驱动胞质刷状缘决定簇和顶端形态发生的极化。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。我们的研究结果确定了肌动球蛋白驱动的形态发生，耦合细胞骨架重组PAR极性信号的顶端起源。
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.
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DOI：
10.1074/jbc.m112.435941
发表时间：
2013-03-22
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Hong L;Kenney SR;Phillips GK;Simpson D;Schroeder CE;Nöth J;Romero E;Swanson S;Waller A;Strouse JJ;Carter M;Chigaev A;Ursu O;Oprea T;Hjelle B;Golden JE;Aubé J;Hudson LG;Buranda T;Sklar LA;Wandinger-Ness A
通讯作者：
Wandinger-Ness A
影响因子：
56.9
作者：
Carlton, Jez G.;Martin-Serrano, Juan
通讯作者：
Martin-Serrano, Juan
影响因子：
64.8
作者：
Mayer, Mirjam;Depken, Martin;Grill, Stephan W.
通讯作者：
Grill, Stephan W.
影响因子：
9.2
作者：
Cheeks, RJ;Canman, JC;Goldstein, B
通讯作者：
Goldstein, B
影响因子：
64.5
作者：
Morais-de-Sá E;Mirouse V;St Johnston D
通讯作者：
St Johnston D