Desmosome

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ΕΤΥΜΟΛΟΓΙΑ

Greek desmos (bond), soma (body) after Josef Schaffer (1920)[1]

The desmosome (maculae adherentes) is the intracellular mechanical junction usually between cells of the same type and interacts with intracellular intermediate filaments. It may be truely distinct only in epithelial cell lines as other cell lines have more complex structures, some of which such as the area composita and complexus adhaerentes were (still are) termed desmosomes due to their structure even though we now know they have extra components. Its protein components can determine both the mechanical but also electrical properties of the junction and hence tissue. There is another type of cellular adhering junction, the adherens junction which interacts with the actin cytoskeleton.

Contents

Components

Schematic of ultrastructure of desmosome. The relationship between plakophilin or plakoglobin and desmoglein or desmocollin is illustrative and does not imply such a relation in life

Key intracellular protein components include:

  1. Plakophilin
  2. Plakoglobin
  3. Pinin

Key transmembrane components include:

  1. Desmoglein
  2. Desmocollin
  3. Perp

These make up a discoid junction with a diameter of about 0.2–0.5 μm which is separated by an intercellular cleft of 24–30 nm. The desmoglein and desmocollin undergo homophilic and heterophilic binding via interaction with the amino-terminal extracellular 1 domain of partner molecules on the same (cis) as well as on the neighbouring cell (trans). The cytoplasmic domains are largely embedded in the outer dense plaque where they are associated with these adaptor proteins plakoglobin and plakophilin. In the inner dense plaque desmoplakin links these adaptor proteins to the intermediate filament cytoskeleton.

More complex desmosome like structures

Myocyte

The cardiac myocyte junction structures apart from adherens junctions and gap junctions are now termed area composita. In 2006 it was discovered that as well as the desmosomal components desmoglein 2, desmocollin 2, desmoplakin and plakophilin-2, the classic adherens junction components N-cadherin, cadherin-11, α-catenin and β-catenin, afadin, vinculin and the tight junction protein ZO-1 were present in all parts of intercalated discs after the first-year postpartum and that plakophilin 2 is of special importance for junction integrity[2].

Lymphatics

The complexus adhaerentes contains desmoplakin and plakoglobin as well as VE-cadherin, α-catenin, β-catenin, afadin as well as the tight junction proteins claudin-5 and ZO-1.Its ultrastructure shares features of both adherens junctions and desmosomes[2].

Meningioma

Have a type of adhering junction that looks like adherens junctions but contains the desmosomal plaque protein plakophilin 2 as well as the classic adherens junction components[2].

Tissue specific components

  • Desmoglein 2, desmocollin 2, desmoplakin, plakoglobin and plakophilin 2 are ubiquitously expressed in all cells with desmosomes.
  • Plakophilin 1 is present in:
    • Stratified epihelium
    • Complex epithelium
  • Plakophilin 3 is present in:
    • Simple epithelium except hepatocytes
    • Stratified epithelium
  • Desmoglein 1 is present in:
    • Mucosa of uterus, stomach, intestine
    • Epithelium of liver and pancreas
  • Desmocollin 1 is present in:
    • Intestine
    • Liver
  • Desmocollin 3 is present in:
    • Stomach
    • Prostate
  • Salivary gland
  • Urothelium
  • Desmoglein 4 is present in:
    • Skin
    • Simple epithelium of pancreas, salivary glands, testis, prostate and liver.
  • Desmoglein 1/desmocollin 1 and desmoglein 3/desmocollin 3 pairs are largely confined to stratified epithelium
    • Stratified corneal epithelium only contains desmoglein 1 and desmocollin 1
  • In the epidermis, plakoglobin, desmoplakin and plakophilin 3 are expressed in all layers but plakophilin 1 is more abundant in the superficial epidermis. Desmoglein 1/desmocollin 1 are predominant in the superficial epidermis, with desmoglein 3/desmocollin 3 predominant in the lower epidermis. In contrast to Dsg 1, which can be detected in some desmosomes in keratinocytes of the basal layer
  • Desmocollin 1 and desmoglein 4 are absent in the basal epidermis layer[2].

Function

Adhesion

Desmosomal adhesion is an Ca2+-dependent interaction between cadherin-type adhesion proteins. The desmosomal cadherins desmoglein and desmocollin are anchored to the intracellular intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic and are subjected to regulation via cellular signalling pathways, which control their molecular composition and thus adhesive properties.

Signalling

Desmosomal components take part in outside-in signalling under physiologic and pathologic conditions.

Pathology

Genetic

Mutations of these components causes congenital conditions such as:

Acquired

There is evidence that mucosal polyps, such as nasal polyps, result from desmosome dysfunction perhaps mediated through weakened desmosomal junctions secondary to inflammatory cytokines[3]

Pemphigus vulgaris is caused by autoantibodies against proteins of the desmosomal adhesion complex. There is downregulation of the desmosomal cadherin desmoglein 3. Perp expression at the membrane is directly disrupted by the autoantibodies, triggering its internalization along with the desmoglein 3[4].

Blistering infective illnesses may be caused by toxins directed towards components of the desmosome.

Historical

First described in the epidermis by the Italian pathologist Bizzozero in 1864. Keith Porter described desmosome ultrastructure in 1956[5]

References

  1. Schaffer J (1920) Vorlesungen über Histologie und Histogenese. Wien.
  2. a b c d Waschke J. The desmosome and pemphigus. Histochemistry and cell biology. 2008 Jul; 130(1):21-54.(Link to article – subscription may be required.)
  3. Zuckerman JD, Lee WY, DelGaudio JM, Moore CE, Nava P, Nusrat A, Parkos CA. Pathophysiology of nasal polyposis: the role of desmosomal junctions. American journal of rhinology. 2008 Nov-Dec; 22(6):589-97.(Link to article – subscription may be required.)
  4. Nguyen B, Dusek RL, Beaudry VG, Marinkovich MP, Attardi LD. Loss of the Desmosomal Protein Perp Enhances the Phenotypic Effects of Pemphigus Vulgaris Autoantibodies. The Journal of investigative dermatology. 2009 Jan 22.(Epub ahead of print) (Link to article – subscription may be required.)
  5. Porter KR. Observations on the fine structure of animal epidermis. In: Proceedings of the International Congress on Electron Microscopy. Royal Microscopical Society, London, p 539. (1956)