Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular strength
Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular strength
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DOI：
10.1016/j.bbamcr.2006.09.018
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发表时间：
2007-05-01
影响因子：
5.1
通讯作者：
Broers, J. L. V.
中科院分区：
文献类型：
--
作者：
Houben, F.;Ramaekers, F. C. S.;Broers, J. L. V.
单个细胞对细胞应激的反应对细胞功能至关重要。从细胞核的结构组分开始，通过细胞骨架细丝到粘附分子和细胞外基质，物理互连的细胞组分的大网络构成了作为支架的整合基质，其允许细胞科普机械应力。除了在机械性能中的作用之外，该网络还在对机械应力的响应中具有机械转导功能。该信号途径不仅调节结构组分如肌动蛋白丝的快速重组，而且还通过NF κ B和其他转录因子刺激例如基因活化。一个完整的机械信号网络的重要性说明了几个遗传缺陷的细胞网络组件，如肌动蛋白，肌营养不良蛋白，结蛋白和核纤层蛋白的生理后果。这些导致受影响的细胞对机械应力的反应受损，并且通常导致受影响的组织的营养不良。最近，细胞核在细胞强度中的重要性已经被确立。一些新的相互连接的蛋白质，如连接核纤层和细胞骨架的nesprins，已被确定。此外，在核纤层蛋白敲除细胞中，核纤层蛋白在决定细胞强度和核稳定性中的功能被说明。核纤层的这些结构组分中缺乏A型纤层蛋白或突变导致对机械应力的细胞反应受损和细胞骨架组织的紊乱。此外，纤层蛋白病显示出与细胞骨架组分中的遗传缺陷引起的疾病所见的临床表型相当的临床表型，进一步表明纤层蛋白在维持细胞的机械性质中起核心作用。(c)2006 Elsevier B.V.保留所有权利。
The response of individual cells to cellular stress is vital for cellular functioning. A large network of physically interconnected cellular components, starting from the structural components of the cells' nucleus, via cytoskeleton filaments to adhesion molecules and the extracellular matrix, constitutes an integrated matrix that functions as a scaffold allowing the cell to cope with mechanical stress. Next to a role in mechanical properties, this network also has a mechanotransductional function in the response to mechanical stress. This signaling route does not only regulate a rapid reorganization of structural components such as actin filaments, but also stimulates for example gene activation via NF kappa B and other transcription factors. The importance of an intact mechano-signaling network is illustrated by the physiological consequences of several genetic defects of cellular network components e.g. actin, dystrophin, desmin and lamins. These give rise to an impaired response of the affected cells to mechanical stress and often result in dystrophy of the affected tissue. Recently, the importance of the cell nucleus in cellular strength has been established. Several new interconnecting proteins, such as the nesprins that link the nuclear lamina to the cytoskeleton, have been identified. Furthermore, the function of nuclear lamins in determining cellular strength and nuclear stability was illustrated in lamin-knock-out cells. Absence of the A-type lamins or mutations in these structural components of the nuclear lamina lead to an impaired cellular response to mechanical stress and disturbances in cytoskeletal organization, In addition, laminopathies show clinical phenotypes comparable to those seen for diseases resulting from genetic defects in cytoskeletal components, further indicating that lamins play a central role in maintaining the mechanical properties of the cell. (c) 2006 Elsevier B.V. All rights reserved.