| Desmosome | |
|---|---|
 A desmosome. | |
 The extracellular core region containing desmocollin and desmoglein, and the plaque contain desmoplakin, which attaches to keratin intermediate filaments. Desmosome is a intercellular junction in animal cell. | |
| Details | |
| Identifiers | |
| Latin | Desmosoma Macula adhaerens |
| MeSH | D003896 |
| TH | H1.00.01.1.02015 |
| FMA | 67412 |
| Anatomical terminology | |
Adesmosome (/ˈdɛzməˌsoʊm/;[1][2]"binding body"), also known as amacula adherens (plural:maculae adherentes) (Latin foradhering spot), is acell structure specialized for cell-to-cell adhesion. A type ofjunctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides ofplasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such ascardiac muscle tissue,bladder tissue,gastrointestinal mucosa, andepithelia.[3]
Desmosomes are composed ofdesmosome-intermediate filament complexes (DIFCs), a network ofcadherin proteins, linker proteins andintermediate filaments.[4] The DIFCs can be broken into three regions: the extracellular core region ("desmoglea"), the outer dense plaque (ODP), and the inner dense plaque (IDP).[3]
The extracellular core region, approximately 34 nm in length, containsdesmoglein anddesmocollin, which are in thecadherin family of cell adhesion proteins. Both have five extracellular domains, and have calcium-binding motifs. Extracellular calcium helps form the cadherin adhesion by allowing the cadherin extracellular domain on desmoglein and desmocollin to become rigid.[5] They bind to each other via heterophilic interactions in the extracellular space near their N-termini, in contrast with the homophilic binding characteristic of other cadherins.[6] Desmoglein and desmocollin have a single pass transmembrane region plus an intracellular anchor to secure its position in the cell membrane. Desmogleins and the desmocollin isoform "Dsc-a" contain an intracellular cadherin domain, which binds toplakoglobin.[3]
The outer dense plaque, which is about 15–20 nm in length, contains the intracellular ends of desmocollin and desmoglein, the N-terminus side ofdesmoplakin, and the armadillo family of mediatory proteinsplakoglobin andplakophilin.[3]Armadillo proteins are involved in mediating attachment to intracellular filaments and cell membrane proteins. Armadillo proteins consist ofβ-catenin,p120-catenin, plakoglobin (γ-catenin), and plakophilins 1-3. In desmosomes, plakoglobin and plakophilin help to anchor desmoplakin and keratin filaments to the desmosome structure. Plakoglobin has 12-arm repeats with a head and tail structure. Plakophilins have 9-arm repeats, and exist in two isoforms: a shorter "a" form and longer "b" form.[citation needed]
The inner dense plaque, also about 15–20 nm in length, contains the C-terminus end of desmoplakin and their attachment to keratin intermediate filaments. Desmoplakin is the most abundant part of the desmosome,[7] as it operates as the mediator between the cadherin proteins in the plasma membrane and the keratin filaments. Desmoplakin has two isoforms that differ in the length of their middle rod domain. All desmoplakins have an N-terminal head, a C-tail consisting of three plakin repeats, and a glycine-serine-arginine rich domain (GSR) at the C-end.[citation needed]
Mutations within the desmosome are the main cause ofarrhythmogenic cardiomyopathy (ACM), a life-threatening disease caused by mutations usually indesmoglein 2, but sometimes indesmocollin 2. It often afflicts individuals between 20 and 50 years, and has been publicly known as a cause of death in young athletes, although the majority of sudden deaths do not occur in close connection to physical activity. The current incidence within the population is accepted as 1/10,000; however, it is thought that 1/200 may have a mutation that may predispose to ACM.[8] Symptoms of ACM include fainting, shortness of breath, and heart palpitations and the condition is treated by implanting a small defibrillator device.
Blistering diseases such as pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune diseases in which auto-antibodies target desmogleins. PV is caused by circulatingautoantibodies (IgG) that targetDsg3 (Desmoglein 3) and sometimesDsg1. PV is manifested by suprabasal acantholysis, or blisters in the mucous membrane and blisters in the epidermis. PF patients have autoantibodies that target Dsg1 with superficial blisters on the epidermis with no mucous membrane issues. Both disease result in a loss of keratinocyte adhesion. Pemphigus can also be caused by a bacterial infection:bullous impetigo is an infection caused by astaphylococcus bacterium that releases a toxin that cleaves the Dsg1 extracellular domain.[citation needed]
Similar symptoms occur with Hailey–Hailey disease, though the cause is not autoimmune but genetic. A haploinsufficiency of the ATP2C1 gene located on chromosome 3, which encodes the protein hSPCA1, causes malformation of the desmosomes.Desmoglein 1 haploinsufficiency leads tostriate palmoplantar keratoderma, a disease which causes extreme thickening of the epidermis. Loss ofdesmoglein 4 leads to defective hair-follicle differentiation.[3]
Epidermolysis bullosa simplex is an epidermal blistering disease caused by mutations in genes coding for keratin 5 and 14, which attach to desmoplakin. This disease manifests as rupture of the basal epidermis when stress is applied.Ectodermal dysplasia orskin fragility syndrome is caused byplakophilin 1 mutations. This is manifested by detachment of intermediate filaments and desmoplakin from the desmosome.[4]
The desmosome was first discovered byGiulio Bizzozero, an Italian pathologist.[3] He named thesedense nodules thenodes of Bizzozero. In 1920, the termdesmosome was originated by Josef Schaffer. The firstcombining form,desmo-,Neo-Latin from Greekdesmos, bond, carries meaning of binding or bonding things together. Combined with-some, which comes fromsoma, body, it thus makes a desmosome abinding body.
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