A keratin code defines the textile nature of epithelial tissue architecture

Di Russo, Jacopo; Magin, Thomas M.; Leube, Rudolf E.

doi:10.1016/j.ceb.2023.102236

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Epithelial cells in homeostasis mechanically couple their cytoskeleton to their basement membrane via integrin receptors 5,44 . Intracellularly, integrin β1 subtypes interface with the actin cytoskeleton via talin, whereas integrin α6β4 binds via plectin the keratin network 45 .…”

Section: Resultsmentioning

confidence: 99%

“…This is different from laminin 332, which additionally supports RPE adhesion via α6β4 integrins, i.e., hemidesmosomes. The role of hemidesmosomes in organizing the keratin network is crucial for the mechanical integrity of epithelial tissues 56,57 and was proposed to define their textile nature 44 . More recently, data from different labs demonstrated that hemidesmosomes and the keratin network reduce cellular traction force 48 and protect the nucleus from mechanical strain 49 .…”

Section: Discussionmentioning

confidence: 99%

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Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

Kozyrina

Piskova

Doolaar

et al. 2023

Preprint

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Epithelial cells are highly interconnected, whereby they acquire mesoscale mechanical properties to accomplish specific tissue functions. In homeostasis, these mechanical features can be summarised as mechanical homeostasis, regulated by the balance of intercellular tension and extracellular matrix adhesion forces. In the outer retina, the significance of these forces in defining its mechanical homeostasis and vision remains poorly understood. The retinal pigmented epithelium (RPE) is located at the base of the retina and supports vision by ensuring the light sensitivity and lifespan of photoreceptor cells. Due to different photoreceptor densities, this functional demand on the RPE varies from the most illuminated macula to the less illuminated retinal periphery and corresponds to a significant difference in monolayer organisation. In this work, we hypothesised that extracellular matrix cues define the relation between RPE organisation, mechanical status and functional demand. We found that the density of basement membrane laminin alpha 5 modulates RPE contractility levels which directly control the epithelium efficiency in phagocyting photoreceptor outer segments. In vivo, laminin alpha 5 density gradient follows retinal functional demand, thus supporting the physiological role of laminin alpha 5 in controlling RPE mechanical homeostasis. ECM-defined mechanical status of the RPE provides a novel parameter to consider for visual function and opens new paths of investigation for sight-threatening diseases such as high myopia and age-related macular degeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

Kozyrina

Piskova

Doolaar

et al. 2023

Preprint

Self Cite

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Plasticity of cytoplasmic intermediate filament architecture determines cellular functions

Schwarz,

Leube

2023

Current Opinion in Cell Biology

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Keratin 16 spatially inhibits type I interferon responses in stressed skin

Cohen,

Xu,

Orosco

et al. 2024

Preprint

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The stress-induced keratin intermediate filament gene/proteinKRT16(K16) is spatially restricted to the suprabasal compartment of the epidermis and extensively used as a biomarker for psoriasis, hidradenitis suppurativa, atopic dermatitis and other inflammatory disorders. However, its role in these conditions remains poorly defined. Here we show that K16 negatively regulates type-I interferon (IFN) signaling and innate immune responses. In mouse skinin vivo,loss ofKrt16leads to exacerbation of imiquimod-induced psoriasiform disease and heightened recruitment of neutrophils in a phorbol ester-induced model of acute sterile inflammation. InKRT16null human keratinocytes, loss of K16 amplifies IFN signaling including phospho-IRF7 and ISG15 after treatment with synthetic dsRNA poly(I:C). Mechanistically, K16 interacts with effectors of the RIG-I-like receptor (RLR) pathway, including 14-3-3ɛ, and inhibits the 14-3-3ɛ:RIG-I interaction upstream of IFN activationin vivoandex vivo. These findings uncover a new paradigm for keratin-dependent regulation of innate immunity, with significant implications for our understanding of inflammatory skin diseases.

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A keratin code defines the textile nature of epithelial tissue architecture

Cited by 3 publications

References 40 publications

Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

Laminin-defined Mechanical Status Modulates Retinal Pigment Epithelium Functionality

Plasticity of cytoplasmic intermediate filament architecture determines cellular functions

Keratin 16 spatially inhibits type I interferon responses in stressed skin

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