Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia

Windoffer, Reinhard; Beil, Michael; Magin, Thomas M.; Leube, Rudolf E.

doi:10.1083/jcb.201008095

Cited by 175 publications

(216 citation statements)

References 160 publications

(232 reference statements)

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“…As squamous differentiation is a terminal event that halts further cell division, 27 preventing this process in confluent BECs might also explain the overlapping layers of epithelial cells following MWCNT exposure. Verifying that MWCNTs affect squamous differentiation in BECs, as well as establishing a mechanism for this interaction, is beyond the scope of this paper; however, it can be speculated that as the cytoskeletal network is heavily involved in cell differentiation, 28 MWCNT interactions with the BEC cytoskeleton might also affect their differentiation. The potential of MWCNTs to impair cell differentiation is an ongoing area of our research.…”

Section: Discussionmentioning

confidence: 99%

Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses

Snyder¹,

Hussain²,

Rice³

et al. 2014

IJN

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Multiwalled carbon nanotubes (MWCNTs) have seen increasing application in consumer products over the past decade, resulting in an increasing risk of human exposure. While numerous toxicological studies have been performed using acute high doses of various carbonaceous nanomaterials, the effects of longer-term, low doses of MWCNTs remain relatively unexplored. This study examined bronchoscopy-derived healthy human bronchial epithelial cells exposed in submerged culture to noncytotoxic doses of MWCNTs over 7 days. Under these conditions, doses as low as 3 μg/mL caused altered cell morphology, superficially resembling fibroblasts. Electrical impedance of the epithelial monolayer was greatly reduced following MWCNT exposure. However, Western blot and polymerase chain reaction showed no elevated expression of the fibroblast markers, vimentin, α-smooth muscle actin, or fibronectin, indicating that a mechanism other than epithelial–mesenchymal transition may be responsible for the changes. Phalloidin and tubulin immunostaining showed disruption of the cytoskeleton, and confocal imaging showed a reduction of the tight junction proteins, zona occludens 1 and occludin. We propose that MWCNTs interfere with the cytoskeleton of the lung epithelium, which can result in a harmful reduction in barrier function over time, even at noncytotoxic doses.

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Section: Discussionmentioning

confidence: 99%

Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses

Snyder¹,

Hussain²,

Rice³

et al. 2014

IJN

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show abstract

“…In addition to posttranslational modifications, the small heat shock protein Hsp27 and proteins of the plakin and S100 families regulate keratin assembly, bundling, and network organization (Windoffer et al 2011;Kayser et al 2013;Bouameur et al 2014;Lesniak and Graczyk-Jarzynka 2015). Plectin is a plakin protein that links keratin bundling to MAPK signaling.…”

Section: Intrinsic Keratin Properties and Associated Proteins As Detementioning

confidence: 99%

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Hatzfeld

Keil

Magin

2017

Cold Spring Harb Perspect Biol

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114

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Adherens junctions (AJs) and desmosomes connect the actin and keratin filament networks of adjacent cells into a mechanical unit. Whereas AJs function in mechanosensing and in transducing mechanical forces between the plasma membrane and the actomyosin cytoskeleton, desmosomes and intermediate filaments (IFs) provide mechanical stability required to maintain tissue architecture and integrity when the tissues are exposed to mechanical stress. Desmosomes are essential for stable intercellular cohesion, whereas keratins determine cell mechanics but are not involved in generating tension. Here, we summarize the current knowledge of the role of IFs and desmosomes in tissue mechanics and discuss whether the desmosome-keratin scaffold might be actively involved in mechanosensing and in the conversion of chemical signals into mechanical strength.

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“…These form a stable network spanning from the cell periphery to the nucleus. Peripheral filaments dynamically enlarge into thicker filaments and progressively intermingle with the preexisting network by continuously moving centripetally until, in the center of the cell, a dense network of keratin filaments encircles the nucleus (8,9).…”

mentioning

confidence: 99%

Keratins as the main component for the mechanical integrity of keratinocytes

Ramms

Fabris

Windoffer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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191

187

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Keratins are major components of the epithelial cytoskeleton and are believed to play a vital role for mechanical integrity at the cellular and tissue level. Keratinocytes as the main cell type of the epidermis express a differentiation-specific set of type I and type II keratins forming a stable network and are major contributors of keratinocyte mechanical properties. However, owing to compensatory keratin expression, the overall contribution of keratins to cell mechanics was difficult to examine in vivo on deletion of single keratin genes. To overcome this problem, we used keratinocytes lacking all keratins. The mechanical properties of these cells were analyzed by atomic force microscopy (AFM) and magnetic tweezers experiments. We found a strong and highly significant softening of keratin-deficient keratinocytes when analyzed by AFM on the cell body and above the nucleus. Magnetic tweezers experiments fully confirmed these results showing, in addition, high viscous contributions to magnetic bead displacement in keratin-lacking cells. Keratin loss neither affected actin or microtubule networks nor their overall protein concentration. Furthermore, depolymerization of actin preserves cell softening in the absence of keratin. On reexpression of the sole basal epidermal keratin pair K5/14, the keratin filament network was reestablished, and mechanical properties were restored almost to WT levels in both experimental setups. The data presented here demonstrate the importance of keratin filaments for mechanical resilience of keratinocytes and indicate that expression of a single keratin pair is sufficient for almost complete reconstitution of their mechanical properties.

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Cytoskeleton in motion: the dynamics of keratin intermediate filaments in epithelia

Cited by 175 publications

References 160 publications

Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses

Multiwalled carbon nanotubes induce altered morphology and loss of barrier function in human bronchial epithelium at noncytotoxic doses

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Keratins as the main component for the mechanical integrity of keratinocytes

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