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

Brosig, Michaela; Ferralli, Jacqueline; Gelman, Laurent; Chiquet, Matthias; Chiquet‐Ehrismann, Ruth

doi:10.1016/j.biocel.2010.07.001

Cited by 97 publications

(97 citation statements)

References 62 publications

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“…While many studies do not differentiate between mechanosensing and mechanoresponses, our study indicates that, based on the initial attachment and alignment of actin fibers, mechanosensing in Lmnadeficient cells seems to be largely intact while the response is not. These data are in line with previous studies showing a defective mechanoresponse due to Lmna mutations or ablation of the LINC complex in 2D and 3D culture systems (Bertrand et al, 2014;Brosig et al, 2010). From these and other studies, it has become clear that both lamin A/C proteins and LINC complex protein disturbances affect mechanoresponsiveness, although a more pronounced effect is seen in cells lacking lamin A and C .…”

Section: Discussionsupporting

confidence: 92%

Cellular strain avoidance is mediated by a functional actin cap; observations in an LMNA-deficient cell model

Tamiello

Halder

Kamps

et al. 2017

Journal of Cell Science

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In adherent cells, the relevance of a physical mechanotransduction pathway provided by the perinuclear actin cap stress fibers has recently emerged. Here, we investigate the impact of a functional actin cap on the cellular adaptive response to topographical cues and uniaxial cyclic strain. Lmna-deficient fibroblasts are used as a model system because they do not develop an intact actin cap, but predominantly form a basal layer of actin stress fibers underneath the nucleus. We observe that topographical cues induce alignment in both normal and Lmna-deficient fibroblasts, suggesting that the topographical signal transmission occurs independently of the integrity of the actin cap. By contrast, in response to cyclic uniaxial strain, Lmna-deficient cells show a compromised strain avoidance response, which is completely abolished when topographical cues and uniaxial strain are applied along the same direction. These findings point to the importance of an intact and functional actin cap in mediating cellular strain avoidance.

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Section: Discussionsupporting

confidence: 92%

Cellular strain avoidance is mediated by a functional actin cap; observations in an LMNA-deficient cell model

Tamiello

Halder

Kamps

et al. 2017

Journal of Cell Science

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“…Recently, experiments with cells lacking proteins of the LINC complex have shown a reduction in force transmission from the cytoskeleton from one side of the nucleus to other side (Brosig et al, 2010;Chancellor et al, 2010) (Jan Lammerding, personal communication). This trans-nuclear cytoskeletal deformation demonstrates the role of the stiff nucleus in propagating forces from the actin cytoskeleton.…”

Section: Perspectivesmentioning

confidence: 99%

Nucleoskeleton mechanics at a glance

Dahl

Kalinowski

2011

Journal of Cell Science

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The nucleus contains the genetic information of the cell and all of the regulatory factors that process the genome effectively. The genome is encapsulated by a dense, filamentous meshwork called the nucleoskeleton, which is located at the inner nuclear membrane. The components of the nucleoskeleton are involved in cellular signaling (Wilson and Berk, 2010), but they are also necessary for maintaining nuclear structure, preventing rupture of the nucleus under force and possibly assisting in force transduction (Wang et al., 2009). Here, we present the integrated mechanical structures of the nucleoskeleton, including lamin filaments, multisubunit proteins, short actin filaments and the genome. We also discuss the integration of mechanical elements from the cytoskeleton into the nucleoskeleton. Based on the mechanical contributions of the individual elements, we demonstrate how mutations in nuclear structures might impact force-dependent etiologies of disease. The accompanying poster aims to provide a translational overview between the cell biology of the nucleus and the biophysics of its underlying polymeric structures.

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“…Recent studies have indicated that muscular dystrophies can be caused by a number of mutations in genes encoding proteins associated with the nuclear envelope (e.g., Lamin A/C, Emerin, and Nesprin encoded by lmna, emd, and syne1, respectively) and their interacting protein partners (3,6,20,30,34,35). Disease-causing mutations in the genes that encode these proteins alter the cellular functions of skeletal muscle (e.g., regeneration, force transmission) and cardiomyocytes, resulting in a variety of observed pathologies (3,4,11,35). Indeed, understanding these proteins is key to unlocking their role(s) both in the physiology of skeletal and cardiac muscle, as well as in the pathology of muscular dystrophies.…”

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confidence: 99%

Lmo7 is dispensable for skeletal muscle and cardiac function

Lao

Esparza

Bremner

et al. 2015

American Journal of Physiology-Cell Physiology

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Emery-Dreifuss muscular dystrophy (EDMD) is a degenerative disease primarily affecting skeletal muscles in early childhood as well as cardiac muscle at later stages. EDMD is caused by a number of mutations in genes encoding proteins associated with the nuclear envelope (e.g., Emerin, Lamin A/C, and Nesprin). Recently, a novel protein, Lim-domain only 7 ( lmo7) has been reported to play a role in the molecular pathogenesis of EDMD. Prior in vitro and in vivo studies suggested the intriguing possibility that Lmo7 plays a role in skeletal or cardiac muscle pathophysiology. To further understand the in vivo role of Lmo7 in striated muscles, we generated a novel Lmo7-null ( lmo7−/−) mouse line. Using this mouse line, we examined skeletal and cardiac muscle physiology, as well as the role of Lmo7 in a model of muscular dystrophy and regeneration using the dystrophin-deficient mdx mouse model. Our results demonstrated that lmo7−/− mice had no abnormalities in skeletal muscle morphology, physiological function, or regeneration. Cardiac function was also unaffected. Moreover, we found that ablation of lmo7 in mdx mice had no effect on the observed myopathy and muscular regeneration exhibited by mdx mice. Molecular analyses also showed no changes in dystrophin complex factors, MAPK pathway components, and Emerin levels in lmo7 knockout mice. Taken together, we conclude that Lmo7 is dispensable for skeletal muscle and cardiac physiology and pathophysiology.

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

Cited by 97 publications

References 62 publications

Cellular strain avoidance is mediated by a functional actin cap; observations in an LMNA-deficient cell model

Cellular strain avoidance is mediated by a functional actin cap; observations in an LMNA-deficient cell model

Nucleoskeleton mechanics at a glance

Lmo7 is dispensable for skeletal muscle and cardiac function

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