Interfering with the connection between the nucleus and the cytoskeleton affects nuclear rotation, mechanotransduction and myogenesis

被引:88
作者
Brosig, Michaela [1 ]
Ferralli, Jacqueline [1 ]
Gelman, Laurent [1 ]
Chiquet, Matthias [2 ]
Chiquet-Ehrismann, Ruth [1 ]
机构
[1] Novartis Res Fdn, Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland
[2] Univ Bern, Dept Orthodont & Dentofacial Orthoped, CH-3010 Bern, Switzerland
关键词
Mechanotransduction; Myogenesis; LINC complex; Stretch; Gene expression; KAPPA-B ACTIVATION; DREIFUSS MUSCULAR-DYSTROPHY; EXTRACELLULAR-MATRIX; MECHANICAL CONTROL; MEMBRANE PROTEIN; GENE-EXPRESSION; TENASCIN-C; DIFFERENTIATION; INDUCTION; ANCHORAGE;
D O I
10.1016/j.biocel.2010.07.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mechanical stress controls a broad range of cellular functions. The cytoskeleton is physically connected to the extracellular matrix via integrin receptors, and to the nuclear lamina by the LINC complex that spans both nuclear membranes. We asked here how disruption of this direct link from the cytoskeleton to nuclear chromatin affects mechanotransduction. Fibroblasts grown on flexible silicone membranes reacted to cyclic stretch by nuclear rotation. This rotation was abolished by inhibition of actomyosin contraction as well as by overexpression of dominant-negative versions of nesprin or sun proteins that form the LINC complex. In an in vitro model of muscle differentiation, cyclic strain inhibits differentiation and induces proliferation of C2C12 myoblasts. Interference with the LINC complex in these cells abrogated their stretch-induced proliferation, while stretch increased p38 MAPK and NFkB phosphorylation and the transcript levels of myogenic transcription factors MyoD and myogenin. We found that the physical link from the cytoskeleton to the nuclear lamina is crucial for correct mechanotransduction, and that disruption of the LINC complex perturbs the mechanical control of cell differentiation. (c) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1717 / 1728
页数:12
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