Cadherin
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Cadherins (Calcium dependant 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]
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[edit] 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.
[edit] 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)
[edit] See also
- Aron Moscona (Identified a class of proteins called cadherins)
- catenin
- protocadherin
- DSC1, DSC2, DSC3 desmocollins
- Desmoglein 1, Desmoglein 2, Desmoglein 3
[edit] References
- ^ Hulpiau P, van Roy F (February 2009). "Molecular evolution of the cadherin superfamily". Int. J. Biochem. Cell Biol. 41 (2): 349–69. doi:. PMID 18848899.
- ^ Angst B, Marcozzi C, Magee A (February 2001). "The cadherin superfamily: diversity in form and function". J Cell Sci 114 (Pt 4): 629-41. PMID 11171368.
- ^ Duguay, D.; A. Foty R.; S. Steinberg M. (2003). "Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants". Dev. Biol. 253: 309–323. doi:.
- ^ Niessen, Carien M.; Gumbiner, Barry M. (2002). "Cadherin-mediated cell sorting not determined by binding or adhesion specificity". The Journal of Cell Biology 156 (2): 389. doi:. PMID 11790800.
- ^ Volk, T.; Cohen, O.; Geiger, B. (1987). "Formation of heterotypic adherens-type junctions between L-CAM containing liver cells and A-CAM containing lens cells". Cell 50: 987–994. doi:.
- ^ Bayas, Marco V.; Leung, Andrew; Evans, Evan; Leckband, Deborah (2005). "Lifetime Measurements Reveal Kinetic Differences between Homophilic Cadherin Bonds". Biophysical Journal 90 (4): 1385. doi:. PMID 16326909.
[edit] Further reading
- Beavon IR (2000). "The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation". Eur. J. Cancer 36 (13 Spec No): 1607–20. doi:. PMID 10959047.
- Berx G, Becker KF, Höfler H, van Roy F (1998). "Mutations of the human E-cadherin (CDH1) gene". Hum. Mutat. 12 (4): 226–37. doi:. PMID 9744472.
- Bryant DM, Stow JL (2005). "The ins and outs of E-cadherin trafficking". Trends Cell Biol. 14 (8): 427–34. doi:. PMID 15308209.
- Chun YS, Lindor NM, Smyrk TC, et al. (2001). "Germline E-cadherin gene mutations: is prophylactic total gastrectomy indicated?". Cancer 92 (1): 181–7. doi:. PMID 11443625.
- Georgolios A, Batistatou A, Manolopoulos L, Charalabopoulos K (2006). "Role and expression patterns of E-cadherin in head and neck squamous cell carcinoma (HNSCC)". J. Exp. Clin. Cancer Res. 25 (1): 5–14. PMID 16761612.
- Hazan RB, Qiao R, Keren R, et al. (2004). "Cadherin switch in tumor progression". Ann. N. Y. Acad. Sci. 1014: 155–63. doi:. PMID 15153430.
- Moran CJ, Joyce M, McAnena OJ (2005). "CDH1 associated gastric cancer: a report of a family and review of the literature". Eur J Surg Oncol 31 (3): 259–64. doi:. PMID 15780560.
- Reynolds AB, Carnahan RH (2005). "Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer". Semin. Cell Dev. Biol. 15 (6): 657–63. doi:. PMID 15561585.
- Wang HD, Ren J, Zhang L (2004). "CDH1 germline mutation in hereditary gastric carcinoma". World J. Gastroenterol. 10 (21): 3088–93. PMID 15457549.
- Wijnhoven BP, Dinjens WN, Pignatelli M (2000). "E-cadherin-catenin cell-cell adhesion complex and human cancer". The British journal of surgery 87 (8): 992–1005. doi:. PMID 10931041.
- Wilson PD (2001). "Polycystin: new aspects of structure, function, and regulation". J. Am. Soc. Nephrol. 12 (4): 834–45. PMID 11274246.
[edit] External links
- Cadherin domain in PROSITE
- The cadherin family
- Online Textbook: "Molecular Biology of the Cell" by Bruce Alberts [1].
- The Cadherin Resource
- IPR002126
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