Cadherin Types and Role in Cell-Cell Adhesion

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.

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

• All Cadherin Content
• What are Cadherins?

Written by

Dr. Surat P

Dr. Surat graduated with a Ph.D. in Cell Biology and Mechanobiology from the Tata Institute of Fundamental Research (Mumbai, India) in 2016. Prior to her Ph.D., Surat studied for a Bachelor of Science (B.Sc.) degree in Zoology, during which she was the recipient of anIndian Academy of SciencesSummer Fellowship to study the proteins involved in AIDs. She produces feature articles on a wide range of topics, such as medical ethics, data manipulation, pseudoscience and superstition, education, and human evolution. She is passionate about science communication and writes articles covering all areas of the life sciences.