Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network

Shroom regulates epithelial cell shape via the apical positioning of an actomyosin network
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DOI:
10.1242/jcs.02626
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发表时间:
2005-11-15
影响因子:
4
通讯作者:
Hildebrand, JD
Hildebrand, JD
中科院分区:
生物学2区
文献类型:
--
作者:
Hildebrand, JD

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肌动蛋白结合蛋白Shroom是多种脊椎动物神经管形态发生所必需的,表明其功能在进化上是保守的。蘑菇通过调节神经上皮细胞的形态来促进神经形成。在体内,蘑菇定位于神经外胚层细胞粘附连接的顶端,在MDCK细胞中定位于顶端连接复合体(AJC)。在极化上皮细胞中诱导Shroom的表达,使顶端收缩,顶端排列和细胞包装显著重组,而不改变顶端-基底极性。这些事件可能模拟体内神经形成所需的细胞形状变化和细胞运动。所观察到的表型取决于蘑菇的能力,改变F-肌动蛋白的分布和调节形成一个以前未知的收缩肌动球蛋白网络与AJC。靶向C末端结构域。的Shroorn的顶端质膜elevening收缩和重组的肌动球蛋白网络,表明该域介导的蘑菇的活动。在体内,蘑菇突变的神经上皮细胞表现出显着减少顶端定位肌球蛋白。因此,蘑菇可能通过调节神经管中肌动球蛋白网络的顶端定位来调节细胞形状变化,从而促进神经管闭合。
The actin-binding protein Shroom is essential for neural tube morphogenesis in multiple vertebrate organisms, indicating its function is evolutionarily conserved. Shroom facilitates neurulation by regulating the morphology of neurepithelial cells. Shroom localizes to the apical tip of adherens junctions of neural ectoderm cells in vivo and to the apical junctional complex (AJC) in MDCK cells. Induced expression of Shroom in polarized epithelia elicits apical constriction and dramatic reorganization of the apical arrangement and packing of cells without altering apical-basal polarity. These events likely mimic the cell shape changes and cellular movements required for neurulation in vivo. The observed phenotypes depend on the ability of Shroom to alter F-actin distribution and regulate the formation of a previously uncharacterized contractile actomyosin network associated with the AJC. Targeting the C-terminal domain. of Shroorn to the apical plasma membrane elicits constriction and reorganization of the actomyosin network, indicting that this domain mediates Shroom's activity. In vivo, Shroom-mutant neural epithelia show a marked reduction in apically positioned myosin. Thus, Shroom likely facilitates neural tube closure by regulating cell shape changes via the apical positioning of an actomyosin network in the neurepithelium.