Cadherin

Cadherins 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. In structure, 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 bind only 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, whereas cells expressing different types of cadherin molecules tend to separate.

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.

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.

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)
* - cadherin 7, type 2
* CDH8 - cadherin 8, type 2
* - cadherin 9, type 2 (T1-cadherin)
* - 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)
* - cadherin 18, type 2
* - cadherin 19, type 2
* - cadherin 20, type 2
* CDH23 - cadherin 23, (neurosensory epithelium)

ee also

*catenin
*protocadherin
*DSC1, DSC2, DSC3 desmocollins
*Desmoglein 1, Desmoglein 2, Desmoglein 3

Further reading

PBB_Further_reading
citations =
*cite journal | author=Berx G, Becker KF, Höfler H, van Roy F |title=Mutations of the human E-cadherin (CDH1) gene |journal=Hum. Mutat. |volume=12 |issue= 4 |pages= 226–37 |year= 1998 |pmid= 9744472 |doi= 10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D
*cite journal | author=Wijnhoven BP, Dinjens WN, Pignatelli M |title=E-cadherin-catenin cell-cell adhesion complex and human cancer |journal=The British journal of surgery |volume=87 |issue= 8 |pages= 992–1005 |year= 2000 |pmid= 10931041 |doi= 10.1046/j.1365-2168.2000.01513.x
*cite journal | author=Beavon IR |title=The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation |journal=Eur. J. Cancer |volume=36 |issue= 13 Spec No |pages= 1607–20 |year= 2000 |pmid= 10959047 |doi= 10.1016/S0959-8049(00)00158-1
*cite journal | author=Wilson PD |title=Polycystin: new aspects of structure, function, and regulation |journal=J. Am. Soc. Nephrol. |volume=12 |issue= 4 |pages= 834–45 |year= 2001 |pmid= 11274246 |doi=
*cite journal | author=Chun YS, Lindor NM, Smyrk TC, "et al." |title=Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated? |journal=Cancer |volume=92 |issue= 1 |pages= 181–7 |year= 2001 |pmid= 11443625 |doi=
*cite journal | author=Hazan RB, Qiao R, Keren R, "et al." |title=Cadherin switch in tumor progression |journal=Ann. N. Y. Acad. Sci. |volume=1014 |issue= |pages= 155–63 |year= 2004 |pmid= 15153430 |doi= 10.1196/annals.1294.016
*cite journal | author=Bryant DM, Stow JL |title=The ins and outs of E-cadherin trafficking |journal=Trends Cell Biol. |volume=14 |issue= 8 |pages= 427–34 |year= 2005 |pmid= 15308209 |doi= 10.1016/j.tcb.2004.07.007
*cite journal | author=Wang HD, Ren J, Zhang L |title=CDH1 germline mutation in hereditary gastric carcinoma |journal=World J. Gastroenterol. |volume=10 |issue= 21 |pages= 3088–93 |year= 2004 |pmid= 15457549 |doi=
*cite journal | author=Reynolds AB, Carnahan RH |title=Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer |journal=Semin. Cell Dev. Biol. |volume=15 |issue= 6 |pages= 657–63 |year= 2005 |pmid= 15561585 |doi= 10.1016/j.semcdb.2004.09.003
*cite journal | author=Moran CJ, Joyce M, McAnena OJ |title=CDH1 associated gastric cancer: a report of a family and review of the literature |journal=Eur J Surg Oncol |volume=31 |issue= 3 |pages= 259–64 |year= 2005 |pmid= 15780560 |doi= 10.1016/j.ejso.2004.12.010
*cite journal | author=Georgolios A, Batistatou A, Manolopoulos L, Charalabopoulos K |title=Role and expression patterns of E-cadherin in head and neck squamous cell carcinoma (HNSCC) |journal=J. Exp. Clin. Cancer Res. |volume=25 |issue= 1 |pages= 5–14 |year= 2006 |pmid= 16761612 |doi=

External links

* [http://www.expasy.org/cgi-bin/nicedoc.pl?PDOC00205 Cadherin domain] in PROSITE
* [http://www.gene.ucl.ac.uk/nomenclature/genefamily/cdh.php The cadherin family]
*Online Textbook: "Molecular Biology of the Cell" by Bruce Alberts [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Search&db=books&doptcmdl=GenBookHL&term=cadherin+AND+mboc4%5Bbook%5D+AND+374326%5Buid%5D&rid=mboc4.section.3508#3518] .
* [http://calcium.uhnres.utoronto.ca/cadherin/pub_pages/general/intro_cadherins.htm The Cadherin Resource]
*InterPro|IPR002126