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Cell and Tissue Research Jun 2015Corneodesmosomes are modified desmosomes present in the stratum corneum (SC). They are crucial for SC cohesion and, thus, constitute one of the pivotal elements of the... (Review)
Review
Corneodesmosomes are modified desmosomes present in the stratum corneum (SC). They are crucial for SC cohesion and, thus, constitute one of the pivotal elements of the functional protective barrier of human skin. Expression of corneodesmosomes and, notably, the process of their degradation are probably altered during several dermatoses leading to the disruption of the permeability barrier or to abnormal, often compensative, SC accumulation. These different situations are reviewed in the present paper.
Topics: Animals; Desmosomes; Epidermis; Genetic Diseases, Inborn; Humans; Models, Biological; Skin Diseases
PubMed: 25378284
DOI: 10.1007/s00441-014-2019-1 -
Current Opinion in Cell Biology Oct 2007Desmosomes are cell-cell junctions responsible for maintaining the structural integrity of tissues by resisting shear forces. Defects result in diseases of mechanically... (Review)
Review
Desmosomes are cell-cell junctions responsible for maintaining the structural integrity of tissues by resisting shear forces. Defects result in diseases of mechanically challenged tissues such as skin and heart. The architectural design represents the key to understanding the strength and durability inherent to desmosomes. A number of different proteins contribute to this architecture, and X-ray crystallography has made considerable progress in defining the atomic structure of various isolated domains. Electron tomography has been used to determine the three-dimensional structure of intact desmosomes in situ. By combining information from X-ray crystallography, cell and molecular biology and electron tomography, it should ultimately be possible to deduce the specific protein interactions that define the mechanical properties of this important adhesive junction.
Topics: Amino Acid Sequence; Animals; Cadherins; Desmoplakins; Desmosomes; Models, Molecular; Molecular Sequence Data; Plakophilins; Protein Conformation; Sequence Alignment; gamma Catenin
PubMed: 17945476
DOI: 10.1016/j.ceb.2007.09.003 -
International Journal of Molecular... Dec 2023Desmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell...
Desmosomes play a key role in the regulation of cell adhesion and signaling. Dysregulation of the desmosome complex is associated with the loss of epithelial cell polarity and disorganized tissue architecture typical of colorectal cancer (CRC). The aim of this study was to investigate and characterize the effect of miR-195-5p on desmosomal junction regulation in CRC. In detail, we proposed to investigate the deregulation of miR-195-5p and , a gene target that encodes a desmosome component in CRC patients. JUP closely interacts with desmosomal cadherins, and downstream, it regulates several intracellular transduction factors. We restored the miR-195-5p levels by transient transfection in colonic epithelial cells to examine the effects of miR-195-5p on JUP mRNA and protein expression. The JUP regulation by miR-195-5p, in turn, determined a modulation of desmosome cadherins (Desmoglein 2 and Desmocollin 2). Furthermore, we focused on whether the miR-195-5p gain of function was also able to modulate the expression of key components of Wnt signaling, such as NLK, LEF1 and Cyclin D1. In conclusion, we have identified a novel mechanism controlled by miR-195-5p in the regulation of adhesive junctions, suggesting its potential clinical relevance for future miRNA-based therapy in CRC.
Topics: Humans; gamma Catenin; Desmosomes; MicroRNAs; Wnt Signaling Pathway; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Cell Proliferation; Protein Serine-Threonine Kinases
PubMed: 38069408
DOI: 10.3390/ijms242317084 -
The Journal of Investigative Dermatology Feb 2024Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to...
Desmosomes are dynamic complex protein structures involved in cellular adhesion. Disruption of these structures by loss-of-function variants in desmosomal genes leads to a variety of skin- and heart-related phenotypes. In this study, we report TUFT1 as a desmosome-associated protein, implicated in epidermal integrity. In two siblings with mild skin fragility, woolly hair, and mild palmoplantar keratoderma but without a cardiac phenotype, we identified a homozygous splice-site variant in the TUFT1 gene, leading to aberrant mRNA splicing and loss of TUFT1 protein. Patients' skin and keratinocytes showed acantholysis, perinuclear retraction of intermediate filaments, and reduced mechanical stress resistance. Immunolabeling and transfection studies showed that TUFT1 is positioned within the desmosome and that its location is dependent on the presence of the desmoplakin carboxy-terminal tail. A Tuft1-knockout mouse model mimicked the patients' phenotypes. Altogether, this study reveals TUFT1 as a desmosome-associated protein, whose absence causes skin fragility, woolly hair, and palmoplantar keratoderma.
Topics: Animals; Humans; Mice; Desmoplakins; Desmosomes; Hair; Hair Diseases; Keratoderma, Palmoplantar; Skin; Skin Abnormalities
PubMed: 37716648
DOI: 10.1016/j.jid.2023.02.044 -
Cell Adhesion & Migration Dec 2024Desmosomes are intercellular junctions that regulate mechanical integrity in epithelia and cardiac muscle. Dynamic desmosome remodeling is essential for wound healing...
Desmosomes are intercellular junctions that regulate mechanical integrity in epithelia and cardiac muscle. Dynamic desmosome remodeling is essential for wound healing and development, yet the mechanisms governing junction assembly remain elusive. While we and others have shown that cadherin ectodomains are highly organized, how this ordered architecture emerges during assembly is unknown. Using fluorescence polarization microscopy, we show that desmoglein 2 (Dsg2) ectodomain order gradually increases during 8 h of assembly, coinciding with increasing adhesive strength. In a scratch wound assay, we observed a similar increase in order in desmosomes assembling at the leading edge of migratory cells. Together, our findings indicate that cadherin organization is a hallmark of desmosome maturity and may play a role in conferring adhesive strength.
Topics: Desmosomes; Desmoglein 2; Cadherins; Intercellular Junctions; Cell Adhesion
PubMed: 38566311
DOI: 10.1080/19336918.2024.2333366 -
Journal of Anatomy Jan 2023For electromechanical coupling of cardiomyocytes, intercalated discs (ICDs) are pivotal as highly specialized intercellular contact areas. ICD consists of adhesive... (Review)
Review
For electromechanical coupling of cardiomyocytes, intercalated discs (ICDs) are pivotal as highly specialized intercellular contact areas. ICD consists of adhesive contacts, such as desmosomes and adherens junctions (AJs) that are partially intermingled and thereby form an area composita to provide mechanical strength, as well as gap junctions (GJ) and sodium channels for excitation propagation. In contrast, in epithelia, mixed junctions with features of desmosomes and AJs are regarded as transitory primarily during the formation of desmosomes. The anatomy of desmosomes is defined by a typical ultrastructure with dense intracellular plaques anchoring the cadherin-type adhesion molecules to the intermediate filament cytoskeleton. Desmosomal diseases characterized by impaired adhesive and signalling functions of desmosomal contacts lead to arrhythmogenic cardiomyopathy when affecting cardiomyocytes and cause pemphigus when manifesting in keratinocytes or present as cardiocutaneous syndromes when both cell types are targeted by the disease, which underscores the high biomedical relevance of these cell contacts. Therefore, comparative analyses regarding the structure and regulation of desmosomal contacts in cardiomyocytes and epithelial cells are helpful to better understand disease pathogenesis. In this brief review, we describe the structural properties of ICD compared to epithelial desmosomes and suggest that mechanisms regulating adhesion may at least in part be comparable. Also, we discuss whether phenomena such as hyperadhesion or the bidirectional regulation of desmosomes to serve as signalling hubs in epithelial cells may also be relevant for ICD.
Topics: Desmosomes; Cell Adhesion; Myocardium; Cadherins; Myocytes, Cardiac
PubMed: 35128661
DOI: 10.1111/joa.13634 -
The Journal of Investigative Dermatology Jan 2016Expression and interaction of desmosomal components and keratins provide stable cell cohesion and protect the epidermis against various types of stress. The...
Expression and interaction of desmosomal components and keratins provide stable cell cohesion and protect the epidermis against various types of stress. The differentiation-specific isotype composition of the keratin cytoskeleton and desmosomes is regarded as a major determinant of adhesive strength. In support, wound healing is characterized by a transient decrease in desmosomal adhesion accompanied by increased expression of keratins K6/K16/K17 at the expense of K1/K10. The significance of altered keratin expression for desmosomal composition and adhesion remains incompletely understood at a mechanistic and functional level. Here, we investigated the respective contribution of K5/K14 or K6/K17 to desmosome adhesion, on their stable re-expression in keratinocytes lacking all keratins. This revealed that K5/K14 filaments support stable desmosomes, whereas "wound healing" keratins K6/K17 induce elevated protein kinase C alpha-mediated desmosome disassembly and subsequent destabilization of epithelial sheets. Moreover, our data suggest that K5/K14 sequester protein kinase C alpha in the cytoplasm, whereas K6/K17 or the absence of all keratins enables protein kinase C alpha translocation to the plasma membrane and induction of desmosome disassembly. Gain- and loss-of-function experiments support a major role of K5 in desmosome stability control via protein kinase C alpha. Our data show that keratin isotypes differently and specifically regulate wound healing and invasion by modulating intercellular adhesion.
Topics: Biotinylation; Blotting, Western; Cell Differentiation; Cell Fractionation; Cells, Cultured; Cytoskeleton; Desmosomes; Epidermal Cells; Epidermis; Gene Silencing; Humans; Keratinocytes; Microscopy, Fluorescence; Protein Kinase C-alpha; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Wound Healing
PubMed: 26763440
DOI: 10.1038/JID.2015.403 -
The Journal of Investigative Dermatology Sep 2016Ca(2+) fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca(2+)... (Review)
Review
Ca(2+) fluxes direct keratinocyte differentiation, cell-to-cell adhesion, migration, and epidermal barrier homeostasis. We previously showed that intracellular Ca(2+) stores constitute a major portion of the calcium gradient especially in the stratum granulosum. Loss of the calcium gradient triggers epidermal barrier homeostatic responses. In this report, using unfixed ex vivo epidermis and human epidermal equivalents we show that endoplasmic reticulum (ER) Ca(2+) is released in response to barrier perturbation, and that this release constitutes the major shift in epidermal Ca(2+) seen after barrier perturbation. We find that ER Ca(2+) release correlates with a transient increase in extracellular Ca(2+). Lastly, we show that ER calcium release resulting from barrier perturbation triggers transient desmosomal remodeling, seen as an increase in extracellular space and a loss of the desmosomal intercellular midline. Topical application of thapsigargin, which inhibits the ER Ca(2+) ATPase activity without compromising barrier integrity, also leads to desmosomal remodeling and loss of the midline structure. These experiments establish the ER Ca(2+) store as a master regulator of the Ca(2+) gradient response to epidermal barrier perturbation, and suggest that ER Ca(2+) homeostasis also modulates normal desmosomal reorganization, both at rest and after acute barrier perturbation.
Topics: Animals; Biopsy, Needle; Calcium; Cell Membrane Permeability; Desmosomes; Endoplasmic Reticulum; Epidermis; Homeostasis; Humans; Immunohistochemistry; Skin Absorption; Thapsigargin
PubMed: 27255610
DOI: 10.1016/j.jid.2016.05.100 -
Trends in Cardiovascular Medicine Oct 2021Arrhythmogenic cardiomyopathy (ACM) is a familial disease, with approximately 60% of patients displaying a pathogenic variant. The majority of genes linked to ACM code... (Review)
Review
Arrhythmogenic cardiomyopathy (ACM) is a familial disease, with approximately 60% of patients displaying a pathogenic variant. The majority of genes linked to ACM code for components of the desmosome: plakophilin-2 (PKP2), desmoglein-2 (DSG2) and desmocollin-2 (DSC2), plakoglobin (JUP) and desmoplakin (DSP). Genetic variants involving the desmosomes are known to cause dysfunction of cell-to-cell adhesions and intercellular gap junctions. In turn, this may result in failure to mechanically hold together the cardiomyocytes, fibrofatty myocardial replacement, cardiac conduction delay and ventricular arrhythmias. It is becoming clearer that pathogenic variants in desmosomal genes such as PKP2 are not only responsible for a mechanical dysfunction of the intercalated disc (ID), but are also the cause of various pro-arrhythmic mechanisms. In this review, we discuss in detail the different molecular interactions associated with desmosomal pathogenic variants, and their contribution to various ACM phenotypes.
Topics: Arrhythmias, Cardiac; Arrhythmogenic Right Ventricular Dysplasia; Desmosomes; Humans; Myocardium; Plakophilins
PubMed: 32738304
DOI: 10.1016/j.tcm.2020.07.006 -
The American Journal of Gastroenterology Jul 2021We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER).
INTRODUCTION
We assessed if obesity perturbs the esophageal epithelial barrier function independent of promotion of gastroesophageal reflux (GER).
METHODS
Thirty-eight participants were divided into 4 groups: Obesity-/GER-, Obesity+/GER-, Obesity-/GER+, and Obesity+/GER+. Esophageal intercellular space and desmosome density (structural integrity) and fluorescein leak (functional integrity) were measured.
RESULTS
The Obesity+/GER- group demonstrated increased intercellular space, reduced desmosome density, and increased fluorescein leak compared with control subjects. These changes were similar but not additive to findings seen in Obesity-/GER + and Obesity+/GER+ patients.
DISCUSSION
Central obesity impairs structural and functional integrity of the esophageal barrier independent of GER, likely predisposing to esophageal injury.
Topics: Adult; Aged; Desmosomes; Esophageal Mucosa; Extracellular Space; Female; Gastroesophageal Reflux; Humans; Male; Middle Aged; Obesity, Abdominal; Permeability
PubMed: 33955725
DOI: 10.14309/ajg.0000000000001196