单丝和角蛋白丝调节上皮小管形态。

IF 2 4区 生物学 Q4 CELL BIOLOGY
Cell structure and function Pub Date : 2018-06-02 Epub Date: 2018-04-28 DOI:10.1247/csf.18010
Ryosuke Nishimura, Kagayaki Kato, Sachiko Fujiwara, Kazumasa Ohashi, Kensaku Mizuno
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引用次数: 6

摘要

上皮小管由上皮细胞片和中央管腔组成,是许多器官的基本结构。机械力在上皮小管形成中起重要作用;然而,对上皮小管形态发生过程中机械力的控制机制知之甚少。Solo(也称为ARHGEF40)是一种靶向RhoA的鸟嘌呤核苷酸交换因子,参与机械力诱导的RhoA激活和应力纤维的形成。Solo与角蛋白8/角蛋白18 (K8/K18)纤维结合,这种相互作用在机械转导中起着至关重要的作用。在这项研究中,我们使用3D胶原凝胶培养的MDCK细胞检测了Solo和K8/K18丝在上皮小管形成中的作用。无论是Solo还是K18的敲低都会导致更圆的小管和更大的管腔,这表明Solo和K8/K18细丝在形成上皮小管的细长形态中起着关键作用。此外,敲低Solo或K18可降低小管管腔和外表面二磷酸化肌球蛋白轻链(一种收缩力的标记物)的水平,这表明Solo和K8/K18细丝参与了上皮小管形态发生过程中肌球蛋白ii介导的收缩力的产生。此外,K18丝通常沿小管长轴取向,但Solo的敲除扰乱了它们的取向。这些结果表明,Solo在上皮小管细长形态的形成以及上皮小管形成过程中肌球蛋白II活性和K18丝组织的调节中发挥了重要作用。关键词:上皮小管形成,Solo,角蛋白,Rho-GEF,肌球蛋白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Solo and Keratin Filaments Regulate Epithelial Tubule Morphology.

Epithelial tubules, consisting of the epithelial cell sheet with a central lumen, are the basic structure of many organs. Mechanical forces play an important role in epithelial tubulogenesis; however, little is known about the mechanisms controlling the mechanical forces during epithelial tubule morphogenesis. Solo (also known as ARHGEF40) is a RhoA-targeting guanine-nucleotide exchange factor that is involved in mechanical force-induced RhoA activation and stress fiber formation. Solo binds to keratin-8/keratin-18 (K8/K18) filaments, and this interaction plays a crucial role in mechanotransduction. In this study, we examined the roles of Solo and K8/K18 filaments in epithelial tubulogenesis using MDCK cells cultured in 3D collagen gels. Knockdown of either Solo or K18 resulted in rounder tubules with increased lumen size, indicating that Solo and K8/K18 filaments play critical roles in forming the elongated morphology of epithelial tubules. Moreover, knockdown of Solo or K18 decreased the level of diphosphorylated myosin light chain (a marker of contractile force) at the luminal and outer surfaces of tubules, suggesting that Solo and K8/K18 filaments are involved in the generation of the myosin II-mediated contractile force during epithelial tubule morphogenesis. In addition, K18 filaments were normally oriented along the long axis of the tubule, but knockdown of Solo perturbed their orientation. These results suggest that Solo plays crucial roles in forming the elongated morphology of epithelial tubules and in regulating myosin II activity and K18 filament organization during epithelial tubule formation.Key words: epithelial tubulogenesis, Solo, keratin, Rho-GEF, myosin.

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来源期刊
Cell structure and function
Cell structure and function 生物-细胞生物学
CiteScore
2.50
自引率
0.00%
发文量
6
审稿时长
>12 weeks
期刊介绍: Cell Structure and Function is a fully peer-reviewed, fully Open Access journal. As the official English-language journal of the Japan Society for Cell Biology, it is published continuously online and biannually in print. Cell Structure and Function publishes important, original contributions in all areas of molecular and cell biology. The journal welcomes the submission of manuscripts on research areas such as the cell nucleus, chromosomes, and gene expression; the cytoskeleton and cell motility; cell adhesion and the extracellular matrix; cell growth, differentiation and death; signal transduction; the protein life cycle; membrane traffic; and organelles.
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