| Literature References | 1. LIAW, C.W., CANNON, C., POWER, M.D., KIBONEKA, P.K. AND RUBIN, L.L.
Identification and cloning of 2 species of cadherins in bovine endothelial
cells.
EMBO J. 9(9) 2701-2708 (1990).
2. GINSBERG, D., DESIMONE, D. AND GEIGER, B.
Expression of a novel cadherin (EP-cadherin) in unfertilized eggs and early
Xenopus embryos.
DEVELOPMENT 111(2) 315-325 (1991).
3. WALSH, F.S., BARTON, C.H., PUTT, W., MOORE, S.E., KELSELL, D., SPURR, N.
AND GOODFELLOW, P.N.
N-Cadherin gene maps to human chromosome 18 and is not linked to the
E-cadherin gene.
J.NEUROCHEM. 55(3) 805-812 (1990).
4. ISHII, K. AND GREEN, K.
Cadherin function: Breaking the barrier.
CURR.BIOL. 11 R569-R572 (2001).
5. GARROD, D., MERRITT, A. AND NIE, Z.
Desmosomal adhesion: structural basis, molecular mechanism and regulation.
MOL.MEMBR.BIOL. 19 81-94 (2002).
6. ANGST, B., MARCOZZI, C. AND MAGEE, A.
The cadherin superfamily: diversity in form and function.
J.CELL SCI. 114 629-641 (2001).
7. KING, I.A., ANGST, B.D., HUNT, D.M., KRUGER, M., ARNEMANN J. AND
BUXTON, R.S.
Hierarchical expression of desmosomal cadherins during stratified epithelial
morphogenesis in the mouse.
DIFFERENTIATION 62 83-96 (1997).
8. MARCOZZI, C., BURDETT I.D., BUXTON, R.S. AND MAGEE, A.I.
Coexpression of both types of desmosomal cadherin and plakoglobin confers
strong intercellular adhesion.
J.CELL SCI. 111 495-509 (1998).
9. AMAGAI, M.
Autoimmunity against desmosomal cadherins in pemphigus.
J.DERMATOL.SCI. 20 92-102 (1999).
10. AMAGAI, M., MATSUYOSHI, N., WANG, Z.H., ANDL, C. AND STANLEY, J.R.
Toxin in bullous impetigo staphylococcal scalded-skin syndrome suggests
targets desmoglein 1.
NATURE MED. 6 1275-1277 (2000).
11. RICKMAN, L., SIMRAK, D., STEVENS, H.P., HUNT, D.M., KING I.A.,
BRYANT, S.P., WADY, R.A., LEIGH, I.M., ARNEMANN, J., MAGEE, A.I.,
KELSELL, D.P. AND BUXTON, R.S.
N-terminal deletion in a desmosomal cadherin causes the autosomal domainat
skin disease striate palmoplantar keratoderma
HUM.MOL.GENET. 8 971-976 (1999).
12. HUNT, D.M., RICKMAN, L., WHITTOCK, N.V., EADY, R.A., SIMRAK, D.,
DOPPING-HEPENSTAL, P.J., STEVENS, H.P., ARMSTRONG, D.K., HENNIES, H.C.,
KUSTER, W., HUGHES, A.E., ARNEMANN, J., LEIGH, I.M., MCGRATH, J.A.,
KELSELL, D.P. AND BUXTON, R.S.
Spectrum of dominant mutations in the desmosomal cadherin desmoglein 1,
causing the skin disease striate palmoplantar keratoderma.
EUR.J.HUM.GENET. 3 197-203 (2001).
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| Documentation | Cadherins, first discovered in mouse teratocarcinoma cells [1], are
structurally and functionally similar molecules [2] that take part in
selective calcium-dependent adhesion interactions between cell surfaces
[3]. 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 [4-6]),
whose extracellular cadherin repeats are responsible for adhesion and whose
intracellular regions interact with intermediate filaments via desmosomal
plaque proteins plakoglobin, plakobilin and desmoplakin [7]. They are
believed to play a wider role in regulation of epithelial differentiation
[5]. 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 [7]. 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 [9]. DSG1 is also the target
of the Staphylococcus aureus blister-causing toxin A [10]. Mutations in DSG1
resulting in reduced levels [11] or extracellularly truncated proteins [12]
are the cause of hepatokeratotic bands on palms and soles, a dominant
inherited disease termed palmoplantar keratoderma.
DESMOGLEIN is a 4-element fingerprint that provides a signature for the
desmogleins. The fingerprint was derived from an initial alignment
of 4 sequences: the motifs were drawn from short conserved regions spanning
the full alignment length, focusing on those sections that characterise
desmogleins but distinguish them from other desmosomal cadherins - motif 1-4
lie in the C-terminal intracellular domain. Two iterations on SPTR40_20f
were required to reach convergence, at which point a true set comprising 5
sequences was identified.
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