Cadherin-Mediated Cell-Cell Interactions

互联网2014-02-13

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Cadherins constitute a family of transmembrane glycoproteins (Table 1 ) that mediate cell-cell adhesion by their ability to self-associate (1 –4 ). For example, E-cadherin binds only to E-cadherin and not to N-cadherin. The homotypic interaction of cadherins is important for the sorting of cells during morphogenesis and for maintaining the normal structure and function of tissues (5 –8 ). Cadherins are highly conserved across species and consist of three domains—i.e., an extracellular domain, transmembrane domain, and intracellular domain. The extracellular domain has multiple calcium-binding regions, which are required for cadherin function. The so-called classical cadherins have five extracellular subdomains (EC1-EC5) with the EC1 domain containing the sequences responsible for self-association and cell-cell adhesion. The intracellular domain is highly conserved across the cadherin family and associates with several proteins collectively termed catenins (9 ,10 ). The catenins mediate linkage of the cadherins to the actin cytoskeleton, a mechanism essential for optimal cadherin activity (11 ).

Table 1 Classical Cadherins and Other Selected Members of the Cadherin Family

Cadherin	cDNA cloned	Tissue distribution
E-Cadherin (uvomorulin, LCAM)	Human, mouse, chicken, Xenopus , Drosophila	Epithelia, skin, osteoclasts, liver, pancreas, kidney, gonads, placenta brain, sensory neurons
N-Cadherin (ACAM)	Human, mouse, bovine, chicken, Xenopus Zebrafish	Brain, notochord, neural tube, somites, skeletal muscle, myocardium, endothelium, mesothelium, ovary, testes, fibroblasts, chondrocytes, inner ear, eye, kidney, pancreas
P-Cadherin	Human, mouse, bovine	Placenta (mouse), skin, breast (myoepithelial cells), prostate (basal cells)
R-Cadherin (cadherin-4)	Human, mouse, chicken, Xenopus	Eye (retina, pigmented epithelium), brain, skeletal muscle, pancreas, gastrointestinal tract
VE-Cadherin (cadherin-5)	Human, mouse, rat	Vascular endothelium Endothelial macrophages
K-Cadherin (cadherin-6)	Human, mouse	Brain, cerebellum, kidney, gastric mucosa, lung, pancreas
Cadherin-7	Chicken
Cadherin-8	Human, mouse, rat	Brain
Cadherin-9	Rat	Brain
Cadherin-10	Chicken, rat	Brain
OB-Cadherin (cadherin-11)	Human, mouse	Osteoblasts, somites, skeletal muscle, fibroblasts
Cadherin-12	Human
T-Cadherin^a (H-cadherin, cadherin-13)	Human, chicken	Nerve, neural crest cells, retina, heart, aorta somite, skeletal muscle, kidney
Cadherin-14	Human
M-Cadherin (cadherin-15)	Human, mouse	Developing skeletal muscle, satellite cells, cerebellum
PB-Cadherin	Rat	Pituitary, brain
B-Cadherin	Chicken	Brain, eye, ear, liver, intestine, bladder, kidney, heart, skeletal muscle, skin
EP-Cadherin (C-cadherin)	Xenopus	Oocytes, unfertilized and fertilized egg, blastula, gastrula, muscle, epidermis
F-Cadherin	Xenopus
XB-Cadherin	Xenopus	Blastula, cement gland, epithelia
Li-Cadherin^a	Rat	Liver, intestine
Ksp-Cadherin^a	Rabbit	Kidney
HPT-1 Cadherin^a,b	Human	Gastrointestinal tract

^a No interaction with catenins. ^b Involved in intestinal peptide transport.