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细丝蛋白的结构、功能与力学特性:细丝蛋白介导的力反应改变是否与人类疾病相关?

Filamin structure, function and mechanics: are altered filamin-mediated force responses associated with human disease?

作者信息

Sutherland-Smith Andrew J

机构信息

Institute of Molecular BioSciences, Massey University, Private Bag 11222, Palmerston North, 4442, New Zealand.

出版信息

Biophys Rev. 2011 Mar;3(1):15-23. doi: 10.1007/s12551-011-0042-y. Epub 2011 Jan 27.

DOI:10.1007/s12551-011-0042-y
PMID:28510233
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5425660/
Abstract

The cytoskeleton framework is essential not only for cell structure and stability but also for dynamic processes such as cell migration, division and differentiation. The F-actin cytoskeleton is mechanically stabilised and regulated by various actin-binding proteins, one family of which are the filamins that cross-link F-actin into networks that greatly alter the elastic properties of the cytoskeleton. Filamins also interact with cell membrane-associated extracellular matrix receptors and intracellular signalling proteins providing a potential mechanism for cells to sense their external environment by linking these signalling systems. The stiffness of the external matrix to which cells are attached is an important environmental variable for cellular behaviour. In order for a cell to probe matrix stiffness, a mechanosensing mechanism functioning via alteration of protein structure and/or binding events in response to external tension is required. Current structural, mechanical, biochemical and human disease-associated evidence suggests filamins are good candidates for a role in mechanosensing.

摘要

细胞骨架框架不仅对细胞结构和稳定性至关重要,而且对诸如细胞迁移、分裂和分化等动态过程也至关重要。F-肌动蛋白细胞骨架通过各种肌动蛋白结合蛋白在机械上得到稳定和调节,其中一类是细丝蛋白,它将F-肌动蛋白交联成网络,极大地改变了细胞骨架的弹性特性。细丝蛋白还与细胞膜相关的细胞外基质受体和细胞内信号蛋白相互作用,通过连接这些信号系统为细胞感知其外部环境提供了一种潜在机制。细胞所附着的外部基质的硬度是影响细胞行为的一个重要环境变量。为了使细胞探测基质硬度,需要一种通过改变蛋白质结构和/或结合事件来响应外部张力的机械传感机制。目前的结构、力学、生化以及与人类疾病相关的证据表明,细丝蛋白是参与机械传感的良好候选者。

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本文引用的文献

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Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion.细丝蛋白 A 调节黏着斑解体,抑制乳腺癌细胞迁移和侵袭。
J Exp Med. 2010 Oct 25;207(11):2421-37. doi: 10.1084/jem.20100433. Epub 2010 Oct 11.
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Actin, a central player in cell shape and movement.肌动蛋白,细胞形状和运动的核心参与者。
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Filamins regulate cell spreading and initiation of cell migration.细丝蛋白调节细胞铺展和细胞迁移的起始。
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Hum Mol Genet. 2009 Dec 15;18(24):4791-800. doi: 10.1093/hmg/ddp442. Epub 2009 Sep 22.
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