| 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).
|
| 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).
DESMOCADHERN is a 4-element fingerprint that provides a signature for the
desmosomal cadherins. The fingerprint was derived from an initial alignment
of 12 sequences: the motifs were drawn from conserved regions spanning the
full alignment length - motif 1 lies in the fourth cadherin repeat in the
N-terminal extracellular domain; motifs 2-4 lie in the C-terminal intra-
cellular domain. Two iterations on SPTR40_20f were required to reach
convergence, at which point a true set comprising 14 sequences was
identified.
|