|TH H1.00.01.1.02015||FMA 67412|
|Latin DesmosomaMacula adhaerens|
A desmosome (/ˈdɛzməˌsoʊm/; "binding body"), also known as a macula adhaerens (plural: maculae adhaerentes) (Latin for adhering spot), is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes.
Desmosomes help to resist shearing forces and are found in simple and stratified squamous epithelium. The intercellular space is very wide (about 30 nm). Desmosomes are also found in muscle tissue where they bind muscle cells to one another.
Desmosomes are molecular complexes of cell adhesion proteins and linking proteins that attach the cell surface adhesion proteins to intracellular keratin cytoskeletal filaments.
The cell adhesion proteins of the desmosome, desmoglein and desmocollin, are members of the cadherin family of cell adhesion molecules. They are transmembrane proteins that bridge the space between adjacent epithelial cells by way of homophilic binding of their extracellular domains to other desmosomal cadherins on the adjacent cell. Both have five extracellular domains, and have calcium-binding vulvae.
The extracellular domain of the desmosome is called the extracellular core domain (ECD) or the desmoglea, and is bisected by an electron-dense midline where the desmoglein and desmocollin proteins bind to each other. These proteins can bind in a W, S, or λ manner.
On the cytoplasmic side of the plasma membrane, there are two dense structures called the outer dense plaque (ODP) and the inner dense plaque (IDP). These are spanned by the desmoplakin protein. The outer dense plaque is where the cytoplasmic domains of the cadherins attach to desmoplakin via plakoglobin and plakophilin. The Inner Dense Plaque is where desmoplakin attaches to the intermediate filaments of the cell.
Arrhythmogenic right ventricular cardiomyopathy
Mutations within the desmosome are the main cause of Arrhythmogenic right ventricular cardiomyopathy (ARVC). It is a life-threatening disease with the molecular underpinnings being the desmosomal constituents (in rank of highest mutation rates) Plakophilin 2, Desmoplakin, Desmoglein-2, Desmocollin 2 and Plakoglobin. It often afflicts (although not exclusive to) young male athletes. 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 ARVC.
If the connecting adjacent epithelial cells of the skin are not functioning correctly, layers of the skin can pull apart and allow abnormal movements of fluid within the skin, resulting in blisters and other tissue damage. Blistering diseases such as Pemphigus vulgaris and Pemphigus foliaceus are autoimmune diseases in which auto-antibodies target the proteins desmoglein 3 and desmoglein 1 respectively. The symptoms of the diseases are caused by the subsequent disruption to the desmosome-keratin filament complex leading to a breakdown in cell adhesion. Similar outbreaks occur with Hailey–Hailey disease, though the cause is not autoimmune, but, rather genetic. A haploinsufficiency of the ATP2C1 gene located on chromosome 3, which encodes the protein hSPCA1, causes malformation of the desmosomes.
The first combining form, desmo-, New Latin from Greek desmos, band, carries meaning of binding or bonding things together. Combined with -some, which comes from soma, body, it thus makes a desmosome a "binding body", a name that aptly describes how desmosomes bind cells together.