Mechanosensitive systems at the cadherin-F-actin interface
Mechanosensitive systems at the cadherin-F-actin interface
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DOI：
10.1242/jcs.109447
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发表时间：
2013-01-15
影响因子：
4
通讯作者：
de Rooij, Johan
中科院分区：
文献类型：
--
作者：
Huveneers, Stephan;de Rooij, Johan
细胞整合生化和机械信息以在多细胞组织中发挥作用。在发育和重塑组织中，机械力包含管理重要细胞过程的指导性信息，包括干细胞的维持、分化和生长。虽然生化和机械诱导的信号转导(蛋白质磷酸化、酶活性的变构调节和结合部位)的原理是相同的，但机械传感的第一步--张力下的蛋白质复合体将物理力的变化转化为细胞信号--是非常不同的，其分子机制才刚刚开始阐明。在这篇评论中，我们将重点放在细胞-细胞连接的机械转导上，旨在了解其中涉及的分子机制。我们描述了不同的连接结构如何与肌动蛋白细胞骨架相关，以及这如何与细胞-细胞连接处的力的大小和方向相关。我们讨论了哪些细胞-细胞黏附受体已经被证明参与了机械转导。然后，我们概述了在细胞-细胞连接的关键机械敏感系统中可能发生的力诱导的分子事件，即钙粘附素-F-肌动蛋白界面，在该界面上，a-连环蛋白和纽蛋白形成了一个中心模块。细胞-细胞连接处的机械转导是一种重要的信号传递机制，我们列举了它与组织发育和疾病的潜在相关性的例子。本文是《关于粘合的迷你焦点》的一部分。欲进一步阅读，请参阅相关文章：由Ronen Zaidel-Bar(J.Cell Sci.)撰写的《钙粘素一目了然》。126、373-378)。Jessica McCormack等人的《用Rho GTPase调节器循环细胞-细胞黏附》。(J.细胞科学)126、379-391)。Marta Canel等人的《E-钙粘素-整合素在癌症侵袭和转移中的串扰》。(J.细胞科学)126、393-401)。
Cells integrate biochemical and mechanical information to function within multicellular tissue. Within developing and remodeling tissues, mechanical forces contain instructive information that governs important cellular processes that include stem cell maintenance, differentiation and growth. Although the principles of signal transduction (protein phosphorylation, allosteric regulation of enzymatic activity and binding sites) are the same for biochemical and mechanical-induced signaling, the first step of mechanosensing, in which protein complexes under tension transduce changes in physical force into cellular signaling, is very different, and the molecular mechanisms are only beginning to be elucidated. In this Commentary, we focus on mechanotransduction at cell-cell junctions, aiming to comprehend the molecular mechanisms involved. We describe how different junction structures are associated with the actomyosin cytoskeleton and how this relates to the magnitude and direction of forces at cell-cell junctions. We discuss which cell-cell adhesion receptors have been shown to take part in mechanotransduction. Then we outline the force-induced molecular events that might occur within a key mechanosensitive system at cell-cell junctions; the cadherin-F-actin interface, at which a-catenin and vinculin form a central module. Mechanotransduction at cell-cell junctions emerges as an important signaling mechanism, and we present examples of its potential relevance for tissue development and disease. This article is part of a Minifocus on Adhesion. For further reading, please see related articles: 'Cadherin adhesome at a glance' by Ronen Zaidel-Bar (J. Cell Sci. 126, 373-378). 'Cycling around cell-cell adhesion with Rho GTPase regulators' by Jessica McCormack et al. (J. Cell Sci. 126, 379-391). 'E-cadherin-integrin crosstalk in cancer invasion and metastasis' by Marta Canel et al. (J. Cell Sci. 126, 393-401).