Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses

Jonca, Nathalie; Leclerc, Emilie; Caubet, Cécile; Simon, Michel; Guerrin, Marina; Serre, Guy

doi:10.1684/ejd.2011.1264

Cited by 57 publications

(56 citation statements)

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“…The ability of CDSN to rescue the adhesion defect induced by filaggrin 2 deficiency (Figure 5) may possibly be accounted for by the fact that CDSN adhesive properties could compensate for the absence of other components of the desmosome such as desmoglein 1 (Jonca et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A

Mohamad

Sarig

Godsel

et al. 2018

Journal of Investigative Dermatology

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Peeling skin syndromes form a large and heterogeneous group of inherited disorders characterized by superficial detachment of the epidermal cornified cell layers, often associated with inflammatory features. Here we report on a consanguineous family featuring noninflammatory peeling of the skin exacerbated by exposure to heat and mechanical stress. Whole exome sequencing revealed a homozygous nonsense mutation in FLG2, encoding filaggrin 2, which cosegregated with the disease phenotype in the family. The mutation was found to result in decreased FLG2 RNA levels as well as almost total absence of filaggrin 2 in the patient epidermis. Filaggrin 2 was found to be expressed throughout the cornified cell layers and to colocalize with corneodesmosin that plays a crucial role in maintaining cell-cell adhesion in this region of the epidermis. The absence of filaggrin 2 in the patient skin was associated with markedly decreased corneodesmosin expression, which may contribute to the peeling phenotype displayed by the patients. Accordingly, using the dispase dissociation assay, we showed that FLG2 downregulation interferes with keratinocyte cell-cell adhesion. Of particular interest, this effect was aggravated by temperature elevation, consistent with the clinical phenotype. Restoration of corneodesmosin levels by ectopic expression rescued cell-cell adhesion. Taken together, the present data suggest that filaggrin 2 is essential for normal cell-cell adhesion in the cornified cell layers.

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Section: Discussionmentioning

confidence: 99%

Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A

Mohamad

Sarig

Godsel

et al. 2018

Journal of Investigative Dermatology

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“…Corneodesmosin is a glycoprotein expressed primarily in the upper layers of the epidermis and hair follicles, where it contributes to keratinocyte cohesion and is a protease target during epidermal desquamation [38]. Another recently discovered desmosome protein with restricted expression is Perp ( p 53 apoptosis e ffector r elated to P MP-22) [39].…”

Section: Desmosome Composition and Architecturementioning

confidence: 99%

Structure, Function, and Regulation of Desmosomes

Kowalczyk¹,

Green²

2013

Progress in Molecular Biology and Translational Science

206

195

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Summary Desmosomes are adhesive intercellular junctions that mechanically integrate adjacent cells by coupling adhesive interactions mediated by desmosomal cadherins to the intermediate filament cytoskeletal network. Desmosomal cadherins are connected to intermediate filaments by densely clustered cytoplasmic plaque proteins comprising members of the armadillo gene family, including plakoglobin and plakophilins, and members of the plakin family of cytolinkers, such as desmoplakin. The importance of desmosomes in tissue integrity is highlighted by human diseases caused by mutations in desmosomal genes, autoantibody attack of desmosomal cadherins, and bacterial toxins that selectively target desmosomal cadherins. In addition to reviewing the well-known roles of desmosomal proteins in tissue integrity, this chapter also highlights the growing appreciation for how desmosomal proteins are integrated with cell signaling pathways to contribute to vertebrate tissue organization and differentiation.

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“…As corneocytes migrate apically, CDs are degraded by extracellular kallikreins (serine proteases) as well as cysteine and aspartate proteases (Brattsand , et al ., 2005, Ovaere , et al ., 2009, Zeeuwen , et al ., 2009, Rawlings, 2010) in a pH-dependent fashion (Hachem , et al ., 2003, Hachem , et al ., 2005, Gunathilake , et al ., 2009), yielding the less-compact stratum disjunctum. The putative biochemical correlates of this sequence include the initial proteolysis of an SC-unique protein, corneodesmosin (Lundstrom , et al ., 1994, Jonca , et al ., 2011), followed by the sequential proteolysis of other CD constituent proteins, including two e-cadherins, desmoglein 1 (DSG1) and desmocollin 1 (DSC1) (Lundstrom , et al ., 1990, Caubet , et al ., 2004). Yet, morphological, biochemical and immunofluorescence studies suggest that CDs, with the possible exception of a subgroup of peripheral CDs (Chapman , et al ., 1990, Haftek, 2006, Ishida-Yamamoto , et al ., 2011), are largely degraded before corneocytes arrive in the outer SC (Rawlings , et al ., 1994).…”

Section: Introductionmentioning

confidence: 99%

Cellular Changes that Accompany Shedding of Human Corneocytes

Lin

Crumrine

Ackerman

et al. 2012

Journal of Investigative Dermatology

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Corneocyte desquamation has been ascribed to either: 1) proteolytic degradation of corneodesmosomes (CD); 2) disorganization of extracellular lamellar bilayers; and/or 3) ‘swell-shrinkage-slough’ (SSS) from hydration/dehydration. To address the cellular basis for normal exfoliation, we compared changes in lamellar bilayer architecture and CD structure in DSquame® strips from the 1st vs. 5th stripping (‘outer’ vs. ‘mid’-stratum corneum [SC], respectively) from 9 normal adult forearms. Strippings were either processed for standard EM or for ruthenium (Ru-V)- or osmium-tetroxide (Os-V) vapor fixation, followed by immediate epoxy embedment, an artifact-free protocol that to our knowledge is previously unreported. CDs are largely intact in the mid-SC, but replaced by electron-dense (hydrophilic) clefts (lacunae) that expand laterally, splitting lamellar arrays in the outer SC. Some undegraded DSG1/DSC1 redistribute uniformly into corneocyte envelopes (CEs) in the outer SC (shown by proteomics, Z-stack confocal imaging and immunoEM). CEs then thicken, likely facilitating exfoliation by increasing corneocyte rigidity. In vapor-fixed images, hydration only altered the volume of the extracellular compartment, expanding lacunae further separating membrane arrays. During dehydration, air replaced water, maintaining the expanded extracellular compartment. Hydration also provoked degradation of membranes by activating contiguous acidic ceramidase activity. Together, these studies identify several parallel mechanisms that orchestrate exfoliation from the surface of normal human skin.

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Corneodesmosomes and corneodesmosin: from the stratum corneum cohesion to the pathophysiology of genodermatoses

Cited by 57 publications

References 0 publications

Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A

Filaggrin 2 Deficiency Results in Abnormal Cell-Cell Adhesion in the Cornified Cell Layers and Causes Peeling Skin Syndrome Type A

Structure, Function, and Regulation of Desmosomes

Cellular Changes that Accompany Shedding of Human Corneocytes

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