Skin Keratins

Wang, Feng-Rong; Zieman, Abigail; Coulombe, Pierre A.

doi:10.1016/bs.mie.2015.09.032

Cited by 59 publications

(62 citation statements)

References 84 publications

(117 reference statements)

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“…Keratinocytes from 1 or 2-day old C57Bl/6 newborn mouse skin were isolated as described (Wang et al 2016), and cultured in FAD medium (low calcium, 0.07mM) for 1 day. Calcium switch experiments (Wang et al 2016) were performed by switching to FAD medium supplemented with with 1 mM CaCl2. Keratinocytes were harvested for analysis at 4 days or at 36 h after calcium switch as indicated in figure legends.…”

Section: Isolation Of Skin Keratinocytes For Primary Culture Calciummentioning

confidence: 99%

Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

Guo

Leacock

Redmond

et al. 2019

Preprint

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SummaryThe type I intermediate filament (IF) keratin 14 (K14) provides vital structural support in basal keratinocytes of epidermis. Recent studies evidenced a role for K14-dependent disulfide bonding in the organization and dynamics of keratin IFs in skin keratinocytes. Here we report that knock-in mice harboring a cysteine-to-alanine substitution at codon 373 (C373A) in Krt14 exhibit alterations in disulfide-bonded K14 species and a barrier defect secondary to enhanced proliferation, faster transit time and altered differentiation in the epidermis. A proteomics screen identified 14-3-3 as major K14 interacting proteins. Follow-up studies showed that YAP1, a transcriptional effector of Hippo signaling regulated by 14-3-3sigma in skin keratinocytes, shows aberrant subcellular partitioning and function in differentiating Krt14C373A keratinocytes. Residue C373 in K14, which is conserved in several other type I IFs, is thus revealed as a novel regulator of keratin organization and YAP function in early differentiating keratinocytes, with an impact on cell mechanics, homeostasis and barrier function in the epidermis.

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Section: Isolation Of Skin Keratinocytes For Primary Culture Calciummentioning

confidence: 99%

Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

Guo

Leacock

Redmond

et al. 2019

Preprint

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“…The clinical importance of desmosomal cadherins is underpinned by severe diseases such as the blister-forming autoimmune skin disease pemphigus, which is a result of autoantibody formation against Dsg3 and Dsg1 and cardiomyopathies caused by genetic variants (Al-Jassar et al, 2013;Hammers and Stanley, 2016). Along the same line, loss-of-function mutations in keratin-encoding genes cause the severe blister-forming disease epidermolysis bullosa simplex (Wang et al, 2016). Mouse models and in vitro studies showed that loss of keratins results in compromised cell cohesion with occurrence of fewer and smaller desmosomes (Bar et al, 2014;Kroger et al, 2013;Loschke et al, 2016;Toivola et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Keratins Regulate the Adhesive Properties of Desmosomal Cadherins through Signaling

Vielmuth

Wanuske

Radeva

et al. 2018

Journal of Investigative Dermatology

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Tightly controlled intercellular adhesion is crucial for the integrity and function of the epidermis. The keratin filament cytoskeleton anchors desmosomes, supramolecular complexes required for strong intercellular adhesion. We tested whether keratin filaments control cell adhesion by regulating the adhesive properties of desmosomal cadherins such as desmoglein (Dsg) 3. Atomic force microscopy and fluorescence recovery after photobleaching experiments showed reduced Dsg3 adhesive forces and membrane stability in murine keratinocytes lacking all keratin filaments. Impairment of the actin cytoskeleton also resulted in decreased Dsg3 immobilization but did not affect Dsg3 binding properties, indicating that the latter are exclusively controlled by keratins. Reduced binding forces were dependent on p38 mitogen-activated protein kinase activity, which was deregulated in keratin-deficient cells. In contrast, inhibition of protein kinase C signaling, which is known to be controlled by keratins, promoted and spatially stabilized Dsg3-mediated interactions in the membrane. These results show a previously unreported mechanism for how keratins stabilize intercellular adhesion on the level of single desmosomal adhesion molecules.

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“…Krt6a/Krt6b heterozygous mating pairs were set up and E18.5 pups were harvested for genotyping. [57]. Tissue sectioning for immunostaining was performed by submerging back skin into OCT (Sakura Finetek), freezing at -20°C, and preparing 5uM sections using the CryoStar NX50 (Thermo Scientific) and stained as described below.…”

Section: Tissue Preparationmentioning

confidence: 99%

A role for keratins in supporting mitochondrial organization and function in skin keratinocytes

Steen

Chen

Wang

et al. 2019

Preprint

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Mitochondria fulfill essential roles in ATP production, metabolic regulation, calcium signaling, generation of reactive oxygen species (ROS) and additional determinants of cellular health. Recent studies have highlighted a role for mitochondria during cell differentiation, including in skin epidermis. Furthermore, the observation of oxidative stress in keratinocytes from Krt16 null mouse skin, a model for pachyonychia congenita (PC) -associated palmoplantar keratoderma, prompted us to examine the role of K16 protein and its partner K6 in regulating the structure and function of mitochondria. Electron microscopy revealed major anomalies in mitochondrial ultrastructure in late stage, E18.5, Krt6 null embryonic mouse skin. Follow-up studies utilizing biochemical, metabolic, and live imaging readouts showed that, relative to controls, skin keratinocytes null for Krt6 or Krt16 exhibit elevated ROS, reduced mitochondrial respiration along with significant alterations in the length, intracellular distribution and movement of mitochondria within the cell. These findings highlight a novel role for K6 and K16 in regulating mitochondrial morphology, dynamics and function and shed new light on the causes of oxidative stress observed in PC and related keratin-based skin disorders.

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Skin Keratins

Cited by 59 publications

References 84 publications

Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

Keratin 14-dependent disulfides regulate epidermal homeostasis and barrier function via 14-3-3σ and YAP1

Keratins Regulate the Adhesive Properties of Desmosomal Cadherins through Signaling

A role for keratins in supporting mitochondrial organization and function in skin keratinocytes

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