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.

Cadherins (Calcium dependent adhesion molecules) are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, ensuring that 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.^[1][2] In structure, they share cadherin repeats, which are the extracellular Ca²⁺-binding domains. There are multiple classes of cadherin molecule, each designated with a prefix (generally noting the type of tissue with which it is associated). It has been observed that cells containing a specific cadherin subtype tend to cluster together to the exclusion of other types, both in cell culture and during development.^{[citation needed]} For example, cells containing N-cadherin tend to cluster with other N-cadherin expressing cells. However, it has been noted that the mixing speed in the cell culture experiments can have an effect on the extent of homotypic specificity.^[3] In addition, several groups have observed heterotypic binding affinity (i.e., binding of different types of cadherin together) in various assays.^[4][5] One current model proposes that cells distinguish cadherin subtypes based on kinetic specificity rather than thermodynamic specificity, as different types of cadherin homotypic bonds have different lifetimes.^[6]

Types

Different members of the cadherin family are found in different locations. E-cadherins are found in epithelial tissue; N-cadherins are found in neurons; and P-cadherins are found in the placenta. T-cadherins have no cytoplasmic domains and must be tethered to the plasma membrane.^{[citation needed]}

E-cadherin (epithelial) is the most well-studied member of the family. 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.^{[citation needed]} 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.^{[citation needed]} 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.^{[citation needed]}

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

Other cadherins

• CDH1 - E-cadherin (epithelial)
• CDH2 - N-cadherin (neural)
• CDH12 - cadherin 12, type 2 (N-cadherin 2)
• CDH3 - P-cadherin (placental)
• CDH4 - R-cadherin (retinal)
• CDH5 - VE-cadherin (vascular endothelial)
• CDH6 - K-cadherin (kidney)
• CDH7 - cadherin 7, type 2
• CDH8 - cadherin 8, type 2
• CDH9 - cadherin 9, type 2 (T1-cadherin)
• CDH10 - cadherin 10, type 2 (T2-cadherin)
• CDH11 - OB-cadherin (osteoblast)
• CDH13 - T-cadherin - H-cadherin (heart)
• CDH15 - M-cadherin (myotubule)
• CDH16 - KSP-cadherin
• CDH17 - LI cadherin (liver-intestine)
• CDH18 - cadherin 18, type 2
• CDH19 - cadherin 19, type 2
• CDH20 - cadherin 20, type 2
• CDH23 - cadherin 23, (neurosensory epithelium)

Human proteins containing cadherin domain

CDH1; CDH10; CDH11; CDH12; CDH13; CDH15; CDH16; CDH17; CDH18; CDH19; CDH2; CDH20; CDH22; CDH23; CDH24; CDH26; CDH28; CDH3; CDH4; CDH5; CDH6; CDH7; CDH8; CDH9; CELSR1; CELSR2; CELSR3; CLSTN1; CLSTN2; CLSTN3; DCHS1; DCHS2; DSC1; DSC2; DSC3; DSG1; DSG2; DSG3; DSG4; FAT; FAT2; FAT4; LOC389118; PCDH1; PCDH10; PCDH11X; PCDH11Y; PCDH12; PCDH15; PCDH17; PCDH18; PCDH19; PCDH20; PCDH7; PCDH8; PCDH9; PCDHA1; PCDHA10; PCDHA11; PCDHA12; PCDHA13; PCDHA2; PCDHA3; PCDHA4; PCDHA5; PCDHA6; PCDHA7; PCDHA8; PCDHA9; PCDHAC1; PCDHAC2; PCDHB1; PCDHB10; PCDHB11; PCDHB12; PCDHB13; PCDHB14; PCDHB15; PCDHB16; PCDHB17; PCDHB18; PCDHB2; PCDHB3; PCDHB4; PCDHB5; PCDHB6; PCDHB7; PCDHB8; PCDHB9; PCDHGA1; PCDHGA10; PCDHGA11; PCDHGA12; PCDHGA2; PCDHGA3; PCDHGA4; PCDHGA5; PCDHGA6; PCDHGA7; PCDHGA8; PCDHGA9; PCDHGB1; PCDHGB2; PCDHGB3; PCDHGB4; PCDHGB5; PCDHGB6; PCDHGB7; PCDHGC3; PCDHGC4; PCDHGC5; PCLKC; RESDA1; RET;

See also

• Aron Moscona (Identified a class of proteins called cadherins)
• catenin
• protocadherin
• DSC1, DSC2, DSC3 desmocollins
• Desmoglein 1, Desmoglein 2, Desmoglein 3

References

Further reading

External links

• Cadherin domain in PROSITE
• The cadherin family
• Online Textbook: "Molecular Biology of the Cell" by Bruce Alberts [1].
• The Cadherin Resource
• IPR002126