Cadherin

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Principal interactions of structural proteins at cadherin-based adherens junction. Actin filaments are linked to α-actinin and to membrane through vinculin. The head domain of vinculin associates to E-cadherin via α-, β - and γ -catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.
Principal interactions of structural proteins at cadherin-based adherens junction. Actin filaments are linked to α-actinin and to membrane through vinculin. The head domain of vinculin associates to E-cadherin via α-, β - and γ -catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.

Cadherins are a class of transmembrane proteins. They play important roles in cell adhesion whereby they ensure cells within tissues are bound together. They are dependent on calcium (Ca2+) ions to function, hence their name.

The cadherin superfamily includes cadherins, protocadherins, desmogleins and desmocollins, and more. Structurally, they share "cadherin repeats", which are the extracellular Ca2+ binding domains. There are multiple classes of cadherin molecule, each designated with a one-letter prefix (generally noting the type of tissue with which it is associated). Cadherins within one class will only bind to themselves. For example, an N-cadherin will bind only to another N-cadherin molecule. Because of this specificity, groups of cells that express the same type of cadherin molecule tend to cluster together during development, while cells expressing different types of cadherin molecules tend to separate.

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[edit] Types

Different members of the cadherin family are found in different locations. E-caderins are found in epithelial tissue; N-cadherins are found in neurons and P-cadherins are found in the placenta.

[edit] E-cadherin

cadherin 1, type 1, E-cadherin (epithelial)
Identifiers
Symbol CDH1 UVO
HUGO 1748
Entrez 999
OMIM 192090
RefSeq NM_004360
UniProt P12830
Other data
Locus Chr. 16 q22.1

E-cadherin (epithelial) is probably the best understood cadherin. It consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and an intracellular domain that binds p120-catenin and beta-catenin. The intracellular domain contains a highly phosphorylated region vital to beta-catenin binding and therefore to E-cadherin function. Beta-catenin can also bind to alpha-catenin. Alpha-catenin participates in regulation of actin-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction. In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5 hour half-life on the cell surface.

Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis. E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.

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