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Cold Spring Harbor Perspectives in... Aug 2009Desmosomes are intercellular junctions that tether intermediate filaments to the plasma membrane. Desmogleins and desmocollins, members of the cadherin superfamily,... (Review)
Review
Desmosomes are intercellular junctions that tether intermediate filaments to the plasma membrane. Desmogleins and desmocollins, members of the cadherin superfamily, mediate adhesion at desmosomes. Cytoplasmic components of the desmosome associate with the desmosomal cadherin tails through a series of protein interactions, which serve to recruit intermediate filaments to sites of desmosome assembly. These desmosomal plaque components include plakoglobin and the plakophilins, members of the armadillo gene family. Linkage to the cytoskeleton is mediated by the intermediate filament binding protein, desmoplakin, which associates with both plakoglobin and plakophilins. Although desmosomes are critical for maintaining stable cell-cell adhesion, emerging evidence indicates that they are also dynamic structures that contribute to cellular processes beyond that of cell adhesion. This article outlines the structure and function of the major desmosomal proteins, and explores the contributions of this protein complex to tissue architecture and morphogenesis.
Topics: Animals; Body Patterning; Calcium; Cell Adhesion; Cell Differentiation; Cytoplasm; Desmoplakins; Desmosomes; Developmental Biology; Drosophila; Epithelium; Humans; Mice; Plakophilins; gamma Catenin
PubMed: 20066089
DOI: 10.1101/cshperspect.a002543 -
Cell and Tissue Research Jun 2015Desmosomes are cell-cell adhesive organelles with a well-known role in forming strong intercellular adhesion during embryogenesis and in adult tissues subject to... (Review)
Review
Desmosomes are cell-cell adhesive organelles with a well-known role in forming strong intercellular adhesion during embryogenesis and in adult tissues subject to mechanical stress, such as the heart and skin. More recently, desmosome components have also emerged as cell signaling regulators. Loss of expression or interference with the function of desmosome molecules results in diseases of the heart and skin and contributes to cancer progression. However, the underlying molecular mechanisms that result in inherited and acquired disorders remain poorly understood. To address this question, researchers are directing their studies towards determining the functions that occur inside and outside of the junctions and the extent to which functions are adhesion-dependent or independent. This review focuses on recent discoveries that provide insights into the role of desmosomes and desmosome components in cell signaling and disease; wherever possible, we address molecular functions within and outside of the adhesive structure.
Topics: Animals; Desmosomes; Disease; Humans; Proteins; Signal Transduction
PubMed: 25693896
DOI: 10.1007/s00441-015-2136-5 -
Trends in Cell Biology Nov 2013Desmosomes are intercellular junctions that anchor intermediate filaments (IFs) to the plasma membrane, forming a supracellular scaffold that provides mechanical... (Review)
Review
Desmosomes are intercellular junctions that anchor intermediate filaments (IFs) to the plasma membrane, forming a supracellular scaffold that provides mechanical resilience to tissues. This anchoring function is accomplished by specialized members of the cadherin family and associated cytoskeletal linking proteins, which together form a highly organized membrane core flanked by mirror-image cytoplasmic plaques. Due to the biochemical insolubility of desmosomes, the mechanisms that govern assembly of these components into a functional organelle remained elusive. Recently developed molecular reporters and live cell imaging approaches have provided powerful new tools to monitor this finely tuned process in real time. Here we discuss studies that are beginning to decipher the machinery and regulation governing desmosome assembly and homeostasis in situ and how these mechanisms are affected during disease pathogenesis.
Topics: Adherens Junctions; Animals; Desmosomes; Homeostasis; Humans
PubMed: 23891292
DOI: 10.1016/j.tcb.2013.06.004 -
Biochimica Et Biophysica Acta.... Sep 2020Desmosomes are cadherin-based adhesion structures that mechanically couple the intermediate filament cytoskeleton of adjacent cells to confer mechanical stress... (Review)
Review
Desmosomes are cadherin-based adhesion structures that mechanically couple the intermediate filament cytoskeleton of adjacent cells to confer mechanical stress resistance to tissues. We have recently described desmosomes as mesoscale lipid raft membrane domains that depend on raft dynamics for assembly, function, and disassembly. Lipid raft microdomains are regions of the plasma membrane enriched in sphingolipids and cholesterol. These domains participate in membrane domain heterogeneity, signaling and membrane trafficking. Cellular structures known to be dependent on raft dynamics include the post-synaptic density in neurons, the immunological synapse, and intercellular junctions, including desmosomes. In this review, we discuss the current state of the desmosome field and put forward new hypotheses for the role of lipid rafts in desmosome adhesion, signaling and epidermal homeostasis. Furthermore, we propose that differential lipid raft affinity of intercellular junction proteins is a central driving force in the organization of the epithelial apical junctional complex.
Topics: Cadherins; Cell Adhesion; Cholesterol; Cytoskeleton; Desmosomes; Epidermis; Humans; Membrane Lipids; Membrane Microdomains; Signal Transduction; Sphingolipids
PubMed: 32376221
DOI: 10.1016/j.bbamem.2020.183329 -
Nature Cell Biology Jun 2023The endoplasmic reticulum (ER) forms a dynamic network that contacts other cellular membranes to regulate stress responses, calcium signalling and lipid transfer. Here,...
The endoplasmic reticulum (ER) forms a dynamic network that contacts other cellular membranes to regulate stress responses, calcium signalling and lipid transfer. Here, using high-resolution volume electron microscopy, we find that the ER forms a previously unknown association with keratin intermediate filaments and desmosomal cell-cell junctions. Peripheral ER assembles into mirror image-like arrangements at desmosomes and exhibits nanometre proximity to keratin filaments and the desmosome cytoplasmic plaque. ER tubules exhibit stable associations with desmosomes, and perturbation of desmosomes or keratin filaments alters ER organization, mobility and expression of ER stress transcripts. These findings indicate that desmosomes and the keratin cytoskeleton regulate the distribution, function and dynamics of the ER network. Overall, this study reveals a previously unknown subcellular architecture defined by the structural integration of ER tubules with an epithelial intercellular junction.
Topics: Desmosomes; Cytoskeleton; Keratins; Intermediate Filaments; Endoplasmic Reticulum
PubMed: 37291267
DOI: 10.1038/s41556-023-01154-4 -
Histochemistry and Cell Biology Jul 2008Desmosomes are patch-like intercellular adhering junctions ("maculae adherentes"), which, in concert with the related adherens junctions, provide the mechanical strength... (Review)
Review
Desmosomes are patch-like intercellular adhering junctions ("maculae adherentes"), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca(2+)-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required.
Topics: Adherens Junctions; Animals; Armadillo Domain Proteins; Cadherins; Desmosomes; Epidermal Cells; Epidermis; Humans; Intermediate Filaments; Keratinocytes; Pemphigus; Plakins
PubMed: 18386043
DOI: 10.1007/s00418-008-0420-0 -
The keratin-desmosome scaffold of internal epithelia in health and disease - The plot is thickening.Current Opinion in Cell Biology Feb 2024Keratin (K) intermediate filaments are attached to desmosomes and constitute the orchestrators of epithelial cell and tissue architecture. While their relevance in the... (Review)
Review
Keratin (K) intermediate filaments are attached to desmosomes and constitute the orchestrators of epithelial cell and tissue architecture. While their relevance in the epidermis is well recognized, our review focuses on their emerging importance in internal epithelia. The significance of keratin-desmosome scaffolds (KDSs) in the intestine is highlighted by transgenic mouse models and individuals with inflammatory bowel disease who display profound KDS alterations. In lung, high K8 expression defines a transitional cell subset during regeneration, and K8 variants are associated with idiopathic pulmonary fibrosis. Inherited variants in desmosomal proteins are overrepresented in idiopathic lung fibrosis, and familiar eosinophilic esophagitis. K18 serum fragments are established hepatocellular injury markers that correlate with the extent of histological inflammation. K17 expression is modified in multiple tumors, and K17 levels might be of prognostic relevance. These data should spur further studies on biological roles of these versatile tissue protectors and efforts on their therapeutic targeting.
Topics: Mice; Animals; Keratins; Desmosomes; Cytoskeleton; Epithelium; Intermediate Filaments
PubMed: 38000362
DOI: 10.1016/j.ceb.2023.102282 -
Biochimica Et Biophysica Acta Mar 2008Desmosomes are intercellular junctions of epithelia and cardiac muscle. They resist mechanical stress because they adopt a strongly adhesive state in which they are said... (Review)
Review
Desmosomes are intercellular junctions of epithelia and cardiac muscle. They resist mechanical stress because they adopt a strongly adhesive state in which they are said to be hyper-adhesive and which distinguishes them from other intercellular junctions; desmosomes are specialised for strong adhesion and their failure can result in diseases of the skin and heart. They are also dynamic structures whose adhesiveness can switch between high and low affinity adhesive states during processes such as embryonic development and wound healing, the switching being signalled by protein kinase C. Desmosomes may also act as signalling centres, regulating the availability of signalling molecules and thereby participating in fundamental processes such as cell proliferation, differentiation and morphogenesis. Here we consider the structure, composition and function of desmosomes, and their role in embryonic development and disease.
Topics: Adhesiveness; Animals; Armadillo Domain Proteins; Biomechanical Phenomena; Cell Adhesion; Desmoplakins; Desmosomal Cadherins; Desmosomes; Embryonic Development; Epithelial Cells; Humans; Intermediate Filaments; Membrane Proteins; Models, Biological; Morphogenesis; Signal Transduction; Stress, Mechanical
PubMed: 17854763
DOI: 10.1016/j.bbamem.2007.07.014 -
Frontiers in Immunology 2018Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells.... (Review)
Review
Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs) 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components. These pathways include Ca, p38MAPK, PKC, Src, EGFR/Erk, and several others. In this review, we delineate the mechanisms relevant for pemphigus pathogenesis based on the histology and the ultrastructure of patients' lesions. We then dissect the mechanisms which can explain the ultrastructural hallmarks detectable in pemphigus patient skin. Finally, we reevaluate the concept that the spectrum of mechanisms, which induce desmosome dysfunction upon binding of pemphigus autoantibodies, finally defines the clinical phenotype.
Topics: Animals; Autoantibodies; Desmosomes; Humans; Pemphigus; Phenotype
PubMed: 29449846
DOI: 10.3389/fimmu.2018.00136 -
Seminars in Cell & Developmental Biology Dec 2004Desmosomes are highly organized intercellular junctions that provide mechanical integrity to tissues by anchoring intermediate filaments to sites of strong adhesion.... (Review)
Review
Desmosomes are highly organized intercellular junctions that provide mechanical integrity to tissues by anchoring intermediate filaments to sites of strong adhesion. Transcriptional regulation of desmosomal cadherins specifies their expression pattern and assembly into junctions of distinct composition, thus tailoring desmosome functions in adhesion and morphogenesis within different cells and complex tissues. Desmosome assembly and disassembly are regulated post-translationally by calcium, kinase/phosphatase activity, proteolytic processing, and cross talk with adherens junctions. Post-translational events also govern the level of non-junctional forms of plakoglobin and plakophilins. These armadillo proteins participate in various nuclear functions, in some cases transducing signals regulating cell growth and differentiation.
Topics: Animals; Armadillo Domain Proteins; Cadherins; Calcium; Cell Adhesion; Cell Adhesion Molecules; Cell Differentiation; Cytoskeletal Proteins; Desmoplakins; Desmosomes; Gap Junctions; Humans; Models, Biological; Protein Processing, Post-Translational; Signal Transduction; Trans-Activators; Transcription, Genetic; gamma Catenin
PubMed: 15561586
DOI: 10.1016/j.semcdb.2004.09.005