Desmosomes

Desmosomes are important adhesive intracellular junctions that link the plasma membrane to the cytoskeleton's intermediate filaments. They are often distributed in areas which are subjected to mechanical stress such as the tissues of the gut and bladder, the myocardium and epithelia. Desmosomes are known for their adhesive properties, however they are also involved in a number of functions such as:

  • Resisting mechanical stress
  • Providing stability and integrity to the tissue structure by providing sites of attachment for cytoskeleton intermediate filaments
  • Mediating cell signalling pathways
  • Roles in tissue morphogenesis, development and differentiation

 

The structural components of desmosomes involves three protein families: desmosomal cadherins, armadillo proteins and plakins.

 

Desmosomal cadherins

Cadherins are important transmembrane proteins that are found in the tissues of both invertebrates and vertebrates. Their main function involves the development, structure and organisation of embryonic tissue. There are multiple classes of cadherins which can be found in various tissues and include the classical and non-classical families.

 

The classical family includes placental (P)-cadherinneural (N)-cadherin and epithelial (E)-cadherin which were the first to be identified. The other two classes include non-classical cadherins such as the desmosomal cadherins (comprised of desmogleins and desmocollins) and proto-cadherins.

 

Desmogleins and desmocollins

Desmosomal cadherins are divided into desmogleins (Dsg 1-4) and desmocollins (Dsc 1-3).  

Their structure consists of a highly conserved series of four extracellular domains (EC) which is followed by a extracellular anchor (EA), then a intracellular anchor (IA).

Desmogleins differ from desmocollins in that they have an intracellular proline-rich linker (IPL), repeat unit domain (RUD), and a desmoglein terminal domain (DTD) absent from desmocollins. Desmocollins exist in two forms; ‘a’ (the typical type) and ‘b’. Desmocollin 'b' lacks the ability to bind plakoblobin (Figure 1)

Both desmocollin 'a' and desmogleins have an intracellular cadherin-like sequence (ICS) which binds plakoglobin.  

 

Figure 1. Desmosomal cadherin structure.

Figure 1. Desmosomla Cadherin structure.

Armadillo proteins

The armadillo protein family consists of plakoglobin (Pg) and plakophilins (Pkps) 1-3 which are present in the nucleus and serve as binding partners for desmosomal cadherins.

Plakoglobin (Pg) is an armadillo protein which has a structurally distinct  amino- (head) and  carboxy- (tail) terminal domains with a 12-arm repeat in between each domain. (Figure 2)

Plakophilins  (PKP1-3) are comprised of 9-arm repeats with an insert between repeats 5 and 6 causing a bend in its structure. PKP1 and PKP2 exist as two forms, each generating a short 'a' form and a longer 'b' form.

 

Figure 2. The plakoglobin (PG) structure



Plakins

Plakins are a family of proteins which link intermediate filaments and the plasma membrane.  There are four types of plakin family members: plectin, desmoplakin, envoplakin and periplakin. The most defined desmosomal associated plakin is the desmoplankin.

Desmoplakin is composed of: a carboxy-terminal tail (C-tail) with three plakin repeat domains or PRD’s A,B and C, glycine-serine-arginine rich domain (GSR), rod domain, and a globular head that mediates binding of armadillo proteins. Desmoplakin exists in two forms (DPI and DPII), the only difference between the two forms is that desmoplakin II is missing two-thirds of its rod domain (Figure 3).

 

Figure 3. Desmoplakin structure



References

Al-Amoudi A, Frangakis AS 2008. Structural studies on desmosomes. Biochem Soc Trans 36:181–187.

Bass-Zubek AE, Green KJ 2007. Biochemical characterization of the desmosome. J Invest Dermatol127:E4–E5.

Green KJ, Jones JC 1996. Desmosomes and hemidesmosomes: Structure and function of molecular components. FASEB J 10:871–881.

Green KJ, Simpson CL 2007. Desmosomes: New perspectives on a classic. J Investig Dermatol127:2499–2515.

Holthofer B, Windoffer R, Troyanovsky S, Leube RE 2007. Structure and function of desmosomes.Int Rev Cytol 264:65–163

Kottke MD, Delva E, Kowalczyk AP 2006. The desmosome: Cell science lessons from human diseases. J Cell Sci 119:797–806

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