Cadherins are Ca2+ dependent cell-cell adhesion molecules that mediate adhesion between cells and tissues in organisms. They are differentiated into several types based on their location and properties.
Classical Cadherins
Cadherins are transmembrane proteins, and the N and C terminal of the cadherins are present in the extracellular and intracellular domain of a cell, respectively. Classical cadherins consist of five cadherin domains which are termed EC1-EC5.
The presence of Ca2+ is critical to bind with the extracellular domain and maintain the stability of the cadherin molecule. Whereas, the intracellular domain binds with several signalling proteins including linkers to the cytoskeletal network. The classical cadherins can also be further sub-divided in to several categories based on their location and function.
Cadherin
E-Cadherin
This cadherin is present in epithelial cells, hence the name ‘E-Cadherin’. Defects in E-Cadherin adhesion have been associated with several diseases, such as cancer, Listeriosis, Candidiasis, Bacteroides infection.
N-Cadherin
This cadherin is present in neurons, fibroblasts, and muscle cells, hence the name ‘N-Cadherin’. Defects in N-Cadherin are associated with cancer (skin, prostate, pancreatic and gastric) and Candidiasis.
P-Cadherin
This cadherin is present widely across the body and defects are associated with cancer, hypotrichosis, ectodermal dysplasia, ectrodactyly, and macular dystrophy.
M-Cadherin
This cadherin in present in skeletal muscle and central nervous system, and the defects in this adhesion are associated with intellectual disabilities.
VE-Cadherin
This cadherin is present in vascular and lymphatic endothelial cell, thus giving its name. Defects in this adhesion are associated with tumor angiogenesis and vascular tumors.
P-Cadherin
P-Cadherins are found in placenta and mutations in this cadherin have been associated with hypotrichosis with juvenile macular dystrophy.
Desmosomal Cadherins
Desmosomes are intercellular cadherins that connect intermediate filaments and cardiac muscle. Desmocollin (Dsc), desmoglein (Dsg), and plakoglobin are three components which form desmosomal adhesion. Dsc and Dsg are approximately 30% identical to each other in terms of amino acid sequence.
Desmocollin
Desmocollins are present in epidermis, hair follicle cells, myocardium, stratified epithelia. The diseases associated with defects in desmocollins are pemphigus vulgaris, hypotrichosis, and IgA pemphigus, among others.
Desmogleins
Desmogleins are present in simple and stratified epithelia, myocardium, hair follicle cells, and the outermost epidermis, among other tissues.
Protocadherins
Protocadherins are transmembrane proteins that can be divided in to ‘clustered’ and ‘non-clustered’ groups.
Clustered group
The clustered group of protocadherins is involved in regulating survival of neurons, and self-avoidance in dendrites. This group consists of protocadherin-β and protocadherin-γ.
The genes that encode for protocadherin-β and protocadherin-γ also contain three constant regions that are present downstream to the exons. Due to this arrangement, a diverse number of protocadherin isoforms can be generated
Non-clustered group
The non-clustered group of protocadherins are involved in promoting motility of a cell. They also mediate other cell processes, including growth cone migration.
Defects in the adhesion mediated by protocadherins is associated with epilepsy and mental retardation. The gene for non-clustered group of protocadherins is present on several chromosomes, and they have been sub-grouped in to δ1 and δ2.
The δ1 sub-group has seven extracellular domains, while δ2 has six extracellular domains. The non-clustered group have functions in early development, axon growth and patterning, synapses, cell-cell adhesion, and cell motility.
Further Reading