Hildebrand Jeffrey D
Department of Biological Sciences, 4249 Fifth Avenue, Crawford Hall, University of Pittsburgh, Pittsburgh, PA 15260, USA.
J Cell Sci. 2005 Nov 15;118(Pt 22):5191-203. doi: 10.1242/jcs.02626. Epub 2005 Oct 25.
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 Shroom 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.
肌动蛋白结合蛋白Shroom对于多种脊椎动物机体的神经管形态发生至关重要,这表明其功能在进化上是保守的。Shroom通过调节神经上皮细胞的形态来促进神经胚形成。在体内,Shroom定位于神经外胚层细胞黏着连接的顶端,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表达Shroom会引发顶端收缩以及细胞顶端排列和堆积的显著重组,而不会改变顶端-基底极性。这些事件可能模拟了体内神经胚形成所需的细胞形状变化和细胞运动。观察到的表型取决于Shroom改变F-肌动蛋白分布以及调节与AJC相关的先前未被描述的收缩性肌动球蛋白网络形成的能力。将Shroom的C末端结构域靶向顶端质膜会引发肌动球蛋白网络的收缩和重组,这表明该结构域介导了Shroom的活性。在体内,Shroom突变的神经上皮细胞显示顶端定位的肌球蛋白显著减少。因此,Shroom可能通过调节神经上皮中肌动球蛋白网络的顶端定位来改变细胞形状,从而促进神经管闭合。