Lulu regulates Shroom-induced apical constriction during neural tube closure.

Lulu regulates Shroom-induced apical constriction during neural tube closure.
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DOI:
10.1371/journal.pone.0081854
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Sokol SY
Sokol SY
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chu CW;Gerstenzang E;Ossipova O;Sokol SY

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顶端收缩是神经管闭合过程中的一种重要细胞行为,但其机制尚未完全清楚。Lulu或EPB4.1l5是一种FERM结构域蛋白,与小鼠胚胎和培养细胞的顶端收缩和肌动球蛋白收缩有关。干扰功能的Lulu在爪蟾胚胎由一个特定的反义吗啉代寡核苷酸或羧基末端片段的Lulu受损的神经板铰链形成过程中的顶端收缩。这种效应可能是由于缺乏肌动球蛋白的收缩性在浅表神经外胚层细胞。相比之下,Lulu RNA在胚胎外胚层细胞中的过度表达引发了异位顶端-基底伸长和顶端收缩,伴随着F-肌动蛋白的顶端募集。内源性Lulu的消耗破坏了Shroom 3的定位和活性,Shroom 3是一种含有PDZ的肌动蛋白结合蛋白,也与顶端收缩有关。此外,Lulu和Shroom 3 RNA合作触发胚胎外胚层的异位顶端收缩。我们的研究结果表明,Lulu是必不可少的Shroom 3依赖的顶端收缩在脊椎动物神经管关闭。
Apical constriction is an essential cell behavior during neural tube closure, but its underlying mechanisms are not fully understood. Lulu, or EPB4.1l5, is a FERM domain protein that has been implicated in apical constriction and actomyosin contractility in mouse embryos and cultured cells. Interference with the function of Lulu in Xenopus embryos by a specific antisense morpholino oligonucleotide or a carboxy-terminal fragment of Lulu impaired apical constriction during neural plate hinge formation. This effect was likely due to lack of actomyosin contractility in superficial neuroectodermal cells. By contrast, overexpression of Lulu RNA in embryonic ectoderm cells triggered ectopic apico-basal elongation and apical constriction, accompanied by the apical recruitment of F-actin. Depletion of endogenous Lulu disrupted the localization and activity of Shroom3, a PDZ-containing actin-binding protein that has also been implicated in apical constriction. Furthermore, Lulu and Shroom3 RNAs cooperated in triggering ectopic apical constriction in embryonic ectoderm. Our findings reveal that Lulu is essential for Shroom3-dependent apical constriction during vertebrate neural tube closure.
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