Nucleoskeleton mechanics at a glance

Dahl, Kris Noel; Kalinowski, Agnieszka

doi:10.1242/jcs.069096

Cited by 78 publications

(94 citation statements)

References 64 publications

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“…Ablation of desmin, a type III IF protein, which homopolymerizes to form the IF cytoskeleton in myocytes, resulted in nuclear mispositioning in mice (Milner et al, 1996), similar to the situation in muscles lacking lamin A (Mejat et al, 2009). Mechanical coupling between the cell membrane, the cytoplasm and the nucleus has been well documented and it emerged in recent years that direct transduction of mechanical forces through the cytoskeleton to the nucleoskeleton is also involved in gene regulation (Dahl and Kalinowski, 2011;Razafsky and Hodzic, 2009). Lamin A and several inner nuclear membrane proteins, such as MAN1, are known to associate with gene regulatory proteins (Stewart et al, 2007).…”

Section: Lack Of Suprabasal Ifs Causes Premature Loss Of Nuclei Durinmentioning

confidence: 92%

Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity

Wallace

Roberts-Thompson

Reichelt

2012

Journal of Cell Science

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SummaryKeratins K1 and K10 are the most abundant proteins in the upper epidermis where they polymerize to form intermediate filaments (IFs). In addition to their well-established function in providing epidermal stability, K1/K10 (i.e. the dimer between K1 and K10) IFs are supposed to be important for terminal epidermal differentiation and barrier formation. It was previously shown that the imbalanced deletion of one of the partner keratins, K10, disturbed epidermal homoeostasis, although stability was provided by compensatory upregulation of K5/K14, which formed IFs together with the remaining K1. Here, we show that deletion of both partner keratins, K1 and K10, results in lethal postnatal skin fragility in mice. Krt1 2/2 ;Krt10 2/2 mice revealed that K1/K10 IFs are unexpectedly dispensable for epidermal stratification. Although the stratum corneum was less compact and cornified envelope differentiation was impaired, a dye exclusion assay showed that the development of a functional water barrier was surprisingly independent from the presence of K1/K10 IFs. The deletion of K1/K10 was not compensated by any other keratin pair such as the basal epidermal keratins K5/K14, and electron microscopy revealed total absence of IFs in the suprabasal epidermis. Although plakoglobin was unchanged, the expression of the desmosomal proteins desmoplakin, desmocollin 1 and desmoglein 1 were altered and suprabasal desmosomes were smaller in Krt1 2/2 ;Krt10 2/2 than in wild-type epidermis suggesting an involvement of K1/K10 IFs in desmosome dynamics. Furthermore, Krt1 2/2 ;Krt10 2/2 mice showed premature loss of nuclei during epidermal differentiation and lower levels of emerin, lamin A/C and Sun1, revealing a previously unknown function for IFs in maintaining nuclear integrity in the upper epidermis.

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Section: Lack Of Suprabasal Ifs Causes Premature Loss Of Nuclei Durinmentioning

confidence: 92%

Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity

Wallace

Roberts-Thompson

Reichelt

2012

Journal of Cell Science

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“…While the nuclear interior is primarily occupied by chromatin, is also contains other distinct structures such as nucleoli and Cajal bodies, as well as structural proteins such as lamins, actin, myosin, titin, and spectrin 23,24 which will be discussed in the following.…”

Section: Overview Of Nuclear Structure and Organizationmentioning

confidence: 99%

The Cellular Mastermind(?)—Mechanotransduction and the Nucleus

Kaminski

Fedorchak

Lammerding

2014

Progress in Molecular Biology and Translational Science

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Cells respond to mechanical stimulation by activation of specific signaling pathways and genes that allow the cell to adapt to its dynamic physical environment. How cells sense the various mechanical inputs and translate them into biochemical signals remains an area of active investigation. Recent reports suggest that the cell nucleus may be directly implicated in this cellular mechanotransduction process. In this chapter, we discuss how forces applied to the cell surface and cytoplasm induce changes in nuclear structure and organization, which could directly affect gene expression, while also highlighting the complex interplay between nuclear structural proteins and transcriptional regulators that may further modulate mechanotransduction signaling. Taken together, these findings paint a picture of the nucleus as a central hub in cellular mechanotransduction—both structurally and biochemically—with important implications in physiology and disease.

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“…It is, therefore, important that externally applied forces can modify nuclear microarchitecture, including chromatin organization and consequently gene expression, much more rapidly than biochemical signaling transduction cascades [103,108,109]. Forces exerted through the ECM on FA integrin receptors catalyze phosphorylation of signaling proteins but are also propagated via the hard-wired cytoskeletal filaments directly to the nucleus, nucleoskeleton [118], and linked chromatin [2,103,119]. …”

Section: External Force Transmission To the Nucleus And Epigeneticmentioning

confidence: 99%

Mechanotransduction Mechanisms for Intraventricular Diastolic Vortex Forces and Myocardial Deformations: Part 2

Pasipoularides

2015

J. of Cardiovasc. Trans. Res.

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Epigenetic mechanisms are fundamental in cardiac adaptations, remodeling, reverse remodeling, and disease. A primary goal of translational cardiovascular research is recognizing whether disease related changes in phenotype can be averted by eliminating or reducing the effects of environmental epigenetic risks. There may be significant medical benefits in using gene-by-environment interaction knowledge to prevent or reverse organ abnormalities and disease. This survey proposes that “environmental” forces associated with diastolic RV/LV rotatory flows exert important, albeit still unappreciated, epigenetic actions influencing functional and morphological cardiac adaptations. Mechanisms analogous to Murray's law of hydrodynamic shear-induced endothelial cell modulation of vascular geometry are likely to link diastolic vortex-associated shear, torque and “squeeze” forces to RV/LV adaptations. The time has come to explore a new paradigm in which such forces play a fundamental epigenetic role, and to work out how heart cells react to them. Findings are considered from various disciplines, imaging modalities, computational fluid dynamics, molecular cell biology and cytomechanics. Examined are, among others, structural dynamics of myocardial cells (endocardium, cardiomyocytes, and fibroblasts), cytoskeleton, nucleoskeleton, and extracellular matrix, mechanotransduction and signaling, and mechanical epigenetic influences on genetic expression. To help integrate and focus relevant pluridisciplinary research, rotatory RV/LV filling flow is placed within a working context that has a cytomechanics perspective. This new frontier in contemporary cardiac research should uncover versatile mechanistic insights linking filling vortex patterns and attendant forces to variable expressions of gene regulation in RV/LV myocardium. In due course, it should reveal intrinsic homeostatic arrangements that support ventricular myocardial function and adaptability.

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Nucleoskeleton mechanics at a glance

Cited by 78 publications

References 64 publications

Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity

Deletion of K1/K10 does not impair epidermal stratification but affects desmosomal structure and nuclear integrity

The Cellular Mastermind(?)—Mechanotransduction and the Nucleus

Mechanotransduction Mechanisms for Intraventricular Diastolic Vortex Forces and Myocardial Deformations: Part 2

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