PR01818

DESMOCADHERN

PRINTS entry
Member databasePRINTS
PRINTS typefamily
Short nameDESMOCADHERN

Description
Imported from IPR009122

Cadherins, first discovered in mouse teratocarcinoma cells
[2]
, are structurally and functionally similar molecules
[3]
that take part in selective calcium-dependent adhesion interactions between cell surfaces
[4]
. There are a number of different isoforms distributed in a tissue-specific manner in a wide variety of organisms. Cells containing different cadherins tend to segregate in vitro, while those that contain the same cadherins tend to preferentially aggregate together. This observation is linked to the finding that cadherin expression causes morphological changes involving the positional segregation of cells into layers, suggesting they may play an important role in the sorting of different cell types during morphogenesis, histogenesis and regeneration. They may also be involved in the regulation of tight and gap junctions, and in the control of intercellular spacing.

Structurally, cadherins comprise a number of domains: these include a signal sequence; a propeptide of ~130 residues; an extracellular domain of ~600 residues; a single transmembrane (TM) domain; and a well-conserved C-terminal cytoplasmic domain of ~150 residues. The extracellular domain can be subdivided into 5 parts, 4 of which are repeats of ~110 residues, and the fifth contains 4 conserved cysteines. The calcium-binding region of cadherins is thought to be located in the extracellular domain.

Desmosomes are localised junctions that hold cells tightly together, common in tissues subject to mechanical strain (e.g., epithelia). Desmosomal cadherins are TM protein components of desmosomes (for review, see
[1, 5, 6]
), whose extracellular cadherin repeats are responsible for adhesion and whose intracellular regions interact with intermediate filaments via desmosomal plaque proteins plakoglobin, plakobilin and desmoplakin. They are believed to play a wider role in regulation of epithelial differentiation. Two sub-families of desmosomal cadherin have been identified, desmocollin (DSC) and desmoglein (DSG).

For each subfamily, three subtypes have been identified, expressed in a cell-type and differentiation-specific manner. Studies in normally desmosome-free cells have shown that expression of at least one DSC and one DSG in combination with plakoglobin is required to promote adhesion
[8]
. Little is known about functional differences between the DSG or DSC sub-families. In sequence, however, DSG differs from DSC in having a longer cytoplasmic region containing DSG repeats.

Desmogleins have been implicated in autoimmune blistering skin lesion diseases. DSG1 has been shown to be a target antigen in pemphigus foliaceous, and DSG3 in pemphigus vulgaris
[7]
. DSG1 is also the target of the Staphylococcus aureus blister-causing toxin A. Mutations in DSG1 resulting in reduced levels or extracellularly truncated proteins are the cause of hepatokeratotic bands on palms and soles, a dominant inherited disease termed palmoplantar keratoderma
[7]
.

References
Imported from IPR009122

1.Cadherin function: breaking the barrier. Ishii K, Green KJ. Curr. Biol. 11, R569-72, (2001). View articlePMID: 11509257

2.Identification and cloning of two species of cadherins in bovine endothelial cells. Liaw CW, Cannon C, Power MD, Kiboneka PK, Rubin LL. EMBO J. 9, 2701-8, (1990). View articlePMID: 2390969

3.Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early Xenopus embryos. Ginsberg D, DeSimone D, Geiger B. Development 111, 315-25, (1991). View articlePMID: 1893866

4.N-cadherin gene maps to human chromosome 18 and is not linked to the E-cadherin gene. Walsh FS, Barton CH, Putt W, Moore SE, Kelsell D, Spurr N, Goodfellow PN. J. Neurochem. 55, 805-12, (1990). View articlePMID: 2384753

5.Desmosomal adhesion: structural basis, molecular mechanism and regulation (Review). Garrod DR, Merritt AJ, Nie Z. Mol. Membr. Biol. 19, 81-94, (2002). View articlePMID: 12126234

6.The cadherin superfamily. Angst BD, Marcozzi C, Magee AI. J. Cell. Sci. 114, 625-6, (2001). View articlePMID: 11171365

7.Desmoglein as a target in autoimmunity and infection. Amagai M. J. Am. Acad. Dermatol. 48, 244-52, (2003). View articlePMID: 12582396

8.Coexpression of both types of desmosomal cadherin and plakoglobin confers strong intercellular adhesion. Marcozzi C, Burdett ID, Buxton RS, Magee AI. J. Cell. Sci. 111 ( Pt 4), 495-509, (1998). PMID: 9443898

Supplementary References

1. Hierarchical expression of desmosomal cadherins during stratified epithelial morphogenesis in the mouse. King IA, Angst BD, Hunt DM, Kruger M, Arnemann J, Buxton RS. Differentiation 62, 83-96, (1997). View articlePMID: 9404003

2. The cadherin superfamily: diversity in form and function. Angst BD, Marcozzi C, Magee AI. J. Cell. Sci. 114, 629-41, (2001). View articlePMID: 11171368

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