Cadherin-Mediated Cell-Cell Interactions
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.
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