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 (named for "calcium-dependent adhesion") are a class of type-1 transmembrane proteins. They play important roles in cell adhesion, forming adherens junctions to bind cells within tissues together. They are dependent on calcium (Ca2+) ions to function, hence their name. Cell-cell adhesion is mediated by extracellular cadherin domains, whereas the intracellular cytoplasmic tail associates with a large number of adaptor and signaling proteins, collectively referred to as the cadherin adhesome.

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 (in general, 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.[3] 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.[4] In addition, several groups have observed heterotypic binding affinity (i.e., binding of different types of cadherin together) in various assays.[5][6] 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.[7]

Structure and Function

Cadherins are synthesized as polypeptides and undergo many post-translational modifications to become the proteins which mediate cell-cell adhesion and recognition.[8] These polypeptides are approximately 720–750 amino acids long. Each cadherin has a small cytoplasmic component, a transmembrane component, and the remaining bulk of the protein is extra-cellular (outside the cell). To date, over 100 types of cadherins in humans have been identified and sequenced.[9]

Development

Cadherins behave as both receptors and ligands for other molecules. During development, their behavior assists in properly positioning cells: they are responsible for the separation of the different tissue layers, and for cellular migration.[10] In the very early stages of development, E-cadherin (epithelial cadherin) is most greatly expressed. During the next stage, the development of the neural plate, N-cadherin (neural cadherin) is expressed and there is a decrease in E-cadherin. Finally, during the development of the notochord and the condensation of somites, E- P- and N-cadherin expression increases. After development, cadherins play a role in maintaining cell and tissue structure, and in cellular movement.[9] Regulation of cadherin expression can occur through promoter methylation among other epigenetic mechanisms.[11]

Tumour metastasis

The E-cadherin - catenin complex plays a key role in cellular adhesion; loss of this function has been associated with greater tumour metastasis.[12]

Types

Cadherin domain
Identifiers
Symbol Cadherin
Pfam PF00028
InterPro IPR002126
SMART CA
PROSITE PDOC00205
SCOP 1nci
SUPERFAMILY 1nci
Ribbon representation of a repeating unit in the extracellular E-cadherin ectodomain of the mouse (Mus Musculus) [13]

There are said to be over 100 different types of cadherins found in vertebrates, which can be classified into four groups: classical, desmosomal, protocadherins, and unconventional.[14][15] This large amount of diversity is accomplished by having multiple cadherin encoding genes combined with alternative RNA splicing mechanisms. Invertebrates contain fewer than 20 types of cadherins.[15]

Classical

Different members of the cadherin family are found in different locations.

  • CDH1 - E-cadherin (epithelial): E-cadherins are found in epithelial tissue
  • CDH2 - N-cadherin (neural): N-cadherins are found in neurons
  • CDH12 - cadherin 12, type 2 (N-cadherin 2)
  • CDH3 - P-cadherin (placental): P-cadherins are found in the placenta.

Desmosomal

Protocadherins

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

FAT; FAT2; FAT4;

Unconventional/ungrouped

  • CDH9 - cadherin 9, type 2 (T1-cadherin)
  • CDH10 - cadherin 10, type 2 (T2-cadherin)
  • CDH4 - R-cadherin (retinal)
  • CDH5 - VE-cadherin (vascular endothelial)
  • CDH6 - K-cadherin (kidney)
  • CDH7 - cadherin 7, type 2
  • CDH8 - cadherin 8, type 2
  • 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)

CDH18; CDH19; CDH20; CDH22; CDH23; CDH24; CDH26; CDH28; CDH4; CDH5; CDH6; CDH7; CDH8; CDH9;

CELSR1; CELSR2; CELSR3; CLSTN1; CLSTN2; CLSTN3; DCHS1; DCHS2; LOC389118;

See also

References

  1. ↑ Lua error in package.lua at line 80: module 'strict' not found.
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  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Harris, Tony J.C., and Ulrich Tepass. "Adherins Junctions: From Molecules to Morphogenesis" Nature Reviews Molecular Cell Biology. 502-514. July 2010. doi:10.1038/nrm2927
  9. ↑ 9.0 9.1 Tepass, Ulrich, et al. "Cadherins in Embryonic and Neural Morphogenisis" Nature Reviews Molecular Cell Biology. November 2000.
  10. ↑ Gumbiner, Barry M. "Regulation of Cadherin-Mediated Adhesion in Morphogenesis" Nature Reviews Molecular Cell Biology. 622-634. August 2005.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ PDB: 3Q2V​; Lua error in package.lua at line 80: module 'strict' not found.; rendered with PyMOL
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ 15.0 15.1 Lua error in package.lua at line 80: module 'strict' not found.

Further reading

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External links

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