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Cadherin-Mediated Cell-Cell Interactions

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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.
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