Lack of Plakoglobin in Epidermis Leads to Keratoderma

Li, Deqiang; Zhang, Wenjun; Liu, Ying; Haneline, Laura S.; Shou, Weinian

doi:10.1074/jbc.m111.299669

Cited by 35 publications

(42 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recently, a point mutation in the keratin-binding domain of DSP was identified as causing SAM syndrome (McAleer et al 2015). Nonsense, as well as splice site mutations, have been observed in PG causing skin fragility, generalized epidermolysis, palmoplantar keratoderma, and woolly hair (Pigors et al 2011;Li et al 2012). Arrhythmogenic cardiomyopathy (AC) is a rare disease of the heart characterized by progressive myocardial dystrophy with fibro-fatty replacement.…”

Section: Evidence From Mouse Models and Human Diseasesmentioning

confidence: 99%

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Hatzfeld

Keil

Magin

2017

Cold Spring Harb Perspect Biol

116

View full text Add to dashboard Cite

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.

show abstract

Section: Evidence From Mouse Models and Human Diseasesmentioning

confidence: 99%

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Hatzfeld

Keil

Magin

2017

Cold Spring Harb Perspect Biol

116

View full text Add to dashboard Cite

show abstract

“…Specifically, gcatenin truncation in its C-terminal is associated with Naxos disease. 6,7,29 However, no hepatic pathology is associated with g-catenin aberrations thus far, other than preliminary observations in liver cancer. 30,31 However, other junctional anomalies, especially in tight junction proteins, have recently been associated with cholestatic liver diseases, like progressive familial intrahepatic cholestasis.…”

Section: G-catenin In Liver Pathophysiologymentioning

confidence: 99%

“…These mice were identified by PCR analysis on genomic DNA for simultaneous presence of floxed alleles (255 bp) and cre-recombinase ( Figure 1A). 6,7 Littermate mice homozygous for floxed g-catenin alleles without any cre, referred to as WT, were used as controls for all studies. Western blot analysis using whole cell lysates from livers of WT and KO showed a notable decrease in g-catenin protein in the KO ( Figure 1B).…”

Section: Generation Of Liver-specific G-catenin Ko Micementioning

confidence: 99%

“…Homozygous g-cateninefloxed mice (C57/BL6 strain) 6,7 and albumin-cre transgenic mice were bred to generate KO mice using a similar breeding strategy, as previously described. 5 Mice with genotype g-catenin loxp/loxp ;Alb-Cre þ/À are KOs.…”

Section: Generation Of Liver-specific G-catenin Conditional Ko Micementioning

confidence: 99%

“…homeostasis through generation of liver-specific KO using the g-cateninefloxed mice 6,7 and albumin-cre transgenic mice, as reported earlier for b-catenin. 5 We show that g-catenin loss in liver is well tolerated, and desmosomes remain intact because of the changes in protein expression of various desmosomal proteins along with their enhanced interactions with b-catenin.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Mice with Hepatic Loss of the Desmosomal Protein γ-Catenin Are Prone to Cholestatic Injury and Chemical Carcinogenesis

Zhou

Pradhan‐Sundd

Poddar

et al. 2015

The American Journal of Pathology

Self Cite

View full text Add to dashboard Cite

.g-Catenin, an important component of desmosomes, may also participate in Wnt signaling. Herein, we dissect the role of g-catenin in liver by generating conditional g-catenin knockout (KO) mice and assessing their phenotype after bile duct ligation (BDL) and diethylnitrosamine-induced chemical carcinogenesis. At baseline, KO and wild-type littermates showed comparable serum biochemistry, liver histology, and global gene expression. b-Catenin protein was modestly increased without any change in Wnt signaling. Desmosomes were maintained in KO, and despite no noticeable changes in gene expression, differential detergent fractionation revealed quantitative and qualitative changes in desmosomal cadherins, plaque proteins, and b-catenin. Enhanced association of b-catenin to desmoglein-2 and plakophilin-3 was observed in KO. When subjected to BDL, wild-type littermates showed specific changes in desmosomal protein expression. In KO, BDL deteriorated baseline compensatory changes, which manifested as enhanced injury and fibrosis. KO also showed enhanced tumorigenesis to diethylnitrosamine treatment because of Wnt activation, as also verified in vitro. g-Catenin overexpression in hepatoma cells increased its binding to T-cell factor 4 at the expense of b-catenineT-cell factor 4 association, induced unique target genes, affected Wnt targets, and reduced cell proliferation and viability. Thus, g-catenin loss in liver is basally well tolerated. However, after insults like BDL, these compensations at desmosomes fail, and KO show enhanced injury. Also, g-catenin negatively regulates tumor growth by affecting Wnt signaling. Plakoglobin or g-catenin belongs to the catenin family of proteins and is a component of desmosomes. Desmosomes are submembranous plaques that provide resistance to mechanical and shear stresses within a tissue and contribute to intercellular adhesion.1 Analogous to b-catenin at adherens junctions (AJs), g-catenin, like other desmosomal plaque proteins, such as desmoplakin (DP) and plakophilin (Pkp), adheres to neighboring cells by linking intracytoplasmic domains of transmembrane desmosomal cadherins like desmoglein (Dsg) and desmocollin (Dsc) to intermediate filaments.1 g-Catenin can also be a structural component of AJ, where it may be exchangeable with its close homolog, b-catenin. Both catenins also contain an armadillo domain and can bind the T-cell factor (TCF) family of transcription factors to participate in Wnt signaling. 2 We have previously identified an increase in g-catenin in the liver-specific b-catenin knockout (KO) mice, 3,4 where it was able to compensate for b-catenin loss at AJs without compromising desmosomes. However, g-catenin did not compensate for b-catenin loss in Wnt signaling, and b-catenin KO continued to lack liver-specific Wnt targets, such as glutamine synthetase (GS) and P450 2e1 and 1a2. 5The primary role of g-catenin in liver pathobiology remains unknown. We addressed the function of g-catenin in liver Supported by NIH grants 1R01DK62277 and 1R01DK100287 and Endowed Chair...

show abstract

Disruption of desmosome function leads to increased centrosome clustering in 14‐3‐3γ‐knockout cells with supernumerary centrosomes

et al. 2021

View full text Add to dashboard Cite

14‐3‐3 proteins are conserved, dimeric, acidic proteins that regulate multiple cellular pathways. Loss of either 14‐3‐3ε or 14‐3‐3γ leads to centrosome amplification. However, we find that while the knockout of 14‐3‐3ε leads to multipolar mitoses, the knockout of 14‐3‐3γ results in centrosome clustering and pseudo‐bipolar mitoses. 14‐3‐3γ knockouts demonstrate compromised desmosome function and a decrease in keratin levels, leading to decreased cell stiffness and an increase in centrosome clustering. Restoration of desmosome function increased multipolar mitoses, whereas knockdown of either plakoglobin or keratin 5 led to decreased cell stiffness and increased pseudo‐bipolar mitoses. These results suggest that the ability of the desmosome to anchor keratin filaments maintains cell stiffness, thus inhibiting centrosome clustering, and that phenotypes observed upon 14‐3‐3 loss reflect the dysregulation of multiple pathways.

show abstract

Lack of Plakoglobin in Epidermis Leads to Keratoderma

Cited by 35 publications

References 26 publications

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics

Mice with Hepatic Loss of the Desmosomal Protein γ-Catenin Are Prone to Cholestatic Injury and Chemical Carcinogenesis

Disruption of desmosome function leads to increased centrosome clustering in 14‐3‐3γ‐knockout cells with supernumerary centrosomes

Contact Info

Product

Resources

About