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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.
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]
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Contents
- 1 Structure and Function
- 2 Types
- 2.1 Classical
- 2.2 Desmosomal
- 2.3 Protocadherins
- 2.4 Unconventional/ungrouped
- 3 See also
- 4 References
- 5 Further reading
- 6 External links
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Structure and Function[edit]
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 80 types of cadherins in humans have been identified and sequenced.[9]
Cadherins behave as both receptors and ligands and 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]
Types[edit]
| Cadherin domain |
| Identifiers |
| Symbol |
Cadherin |
| Pfam |
PF00028 |
| InterPro |
IPR002126 |
| SMART |
CA |
| PROSITE |
PDOC00205 |
| SCOP |
1nci |
| SUPERFAMILY |
1nci |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe |
| PDBsum |
structure summary |
|
Ribbon representation of a repeating unit in the extracellular E-cadherin ectodomain of the mouse (
Mus Musculus)
[11]
Cadherins can be classified into four groups: classical, desmosomal, protocadherins, and unconventional.[12]
Classical[edit]
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[edit]
- Desmoglein (DSG1, DSG2, DSG3, DSG4)
- Desmocollin (DSC1, DSC2, DSC3)
Protocadherins[edit]
- 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
FAT; FAT2; FAT4;
Unconventional/ungrouped[edit]
- 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)
- CDH10; CDH11; CDH13; CDH15; CDH16; CDH17;
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[edit]
- Aron Moscona (Identified a class of proteins called cadherins)
- Catenin
- List of target antigens in pemphigus
References[edit]
- ^ Hulpiau P, van Roy F (February 2009). "Molecular evolution of the cadherin superfamily". Int. J. Biochem. Cell Biol. 41 (2): 349–69. doi:10.1016/j.biocel.2008.09.027. 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.
- ^ Bello S.M., Millo H., Rajebhosale M., Price S.R. (2012) Catenin-dependent cadherin function drives divisional segregation of spinal chord motor neurons. J. Neuroscience 32(2):490-505
- ^ Duguay, D.; A. Foty R., RA; S. Steinberg M., MS (2003). "Cadherin-mediated cell adhesion and tissue segregation: qualitative and quantitative determinants". Dev. Biol. 253 (2): 309–323. doi:10.1016/S0012-1606(02)00016-7. PMID 12645933.
- ^ 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): 389–399. doi:10.1083/jcb.200108040. PMC 2199232. 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 (6): 987–994. doi:10.1016/0092-8674(87)90525-3. PMID 3621349.
- ^ Bayas, Marco V.; Leung, Andrew; Evans, Evan; Leckband, Deborah (2005). "Lifetime Measurements Reveal Kinetic Differences between Homophilic Cadherin Bonds". Biophysical Journal 90 (4): 1385–95. doi:10.1529/biophysj.105.069583. PMC 1367289. PMID 16326909.
- ^ 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.
- ^ a b Tepass, Ulrich, et al. "Cadherins in Embryonic and Neural Morphogenisis" Nature Reviews Molecular Cell Biology. November 2000.
- ^ Gumbiner, Barry M. "Regulation of Cadherin-Mediated Adhesion in Morphogenesis" Nature Reviews Molecular Cell Biology. 622-634. August 2005.
- ^ PDB 3Q2V; Harrison, O.J., Jin, X., Hong, S., Bahna, F., Ahlsen, G., Brasch, J., Wu, Y., Vendome, J., Felsovalyi, K., Hampton, C.M., Troyanovsky, R.B., Ben-Shaul, A., Frank, J., Troyanovsky, S.M., Shapiro, L., Honig, B. (2011). "The extracellular architecture of adherens junctions revealed by crystal structures of type I cadherins". Structure 19 (2): 244–56. doi:10.1016/j.str.2010.11.016. PMC 3070544. PMID 21300292. ; rendered with PyMOL
- ^ Stefan Offermanns; Walter Rosenthal (2008). Encyclopedia of Molecular Pharmacology. Springer. pp. 306–. ISBN 978-3-540-38916-3. Retrieved 14 December 2010.
Further reading[edit]
- 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:10.1016/S0959-8049(00)00158-1. 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:10.1002/(SICI)1098-1004(1998)12:4<226::AID-HUMU2>3.0.CO;2-D. PMID 9744472.
- Bryant DM, Stow JL (2005). "The ins and outs of E-cadherin trafficking". Trends Cell Biol. 14 (8): 427–34. doi:10.1016/j.tcb.2004.07.007. 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:10.1002/1097-0142(20010701)92:1<181::AID-CNCR1307>3.0.CO;2-J. 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:10.1196/annals.1294.016. 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:10.1016/j.ejso.2004.12.010. 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:10.1016/j.semcdb.2004.09.003. 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:10.1046/j.1365-2168.2000.01513.x. PMID 10931041.
- Wilson PD (2001). "Polycystin: new aspects of structure, function, and regulation". J. Am. Soc. Nephrol. 12 (4): 834–45. PMID 11274246.
- Renaud-Young M, Gallin WJ (2002). "In the first extracellular domain of E-cadherin, heterophilic interactions, but not the conserved His-Ala-Val motif, are required for adhesion". Journal of Biological Chemistry 277 (42): 39609–39616. doi:10.1074/jbc.M201256200. PMID 12154084.
External links[edit]
- Proteopedia Cadherin - view cadherin structure in interactive 3D
- Cadherin domain in PROSITE
- The cadherin family
- Alberts, Bruce. Molecular Biology of the Cell
- The Cadherin Resource
- IPR002126
- [1]
- “Cadherin adhesome at a glance”. J Cell Sci 126, 373-378
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Membrane proteins: cell adhesion molecules
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| Calcium-independent |
| IgSF CAM |
- N-CAM (Myelin protein zero)
- ICAM (1, 5)
- VCAM-1
- PE-CAM
- L1-CAM
- Nectin (PVRL1, PVRL2, PVRL3)
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| Integrins |
- LFA-1 (CD11a+CD18)
- Integrin alphaXbeta2 (CD11c+CD18)
- Macrophage-1 antigen (CD11b+CD18)
- VLA-4 (CD49d+CD29)
- Glycoprotein IIb/IIIa (ITGA2B+ITGB3)
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| Calcium-dependent |
| Cadherins |
| Classical |
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| Desmosomal |
- Desmoglein (DSG1, DSG2, DSG3, DSG4)
- Desmocollin (DSC1, DSC2, DSC3)
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| Protocadherin |
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| Unconventional/ungrouped |
- T-cadherin
- CDH4
- CDH5
- CDH6
- CDH8
- CDH11
- CDH12
- CDH15
- CDH16
- CDH17
- CDH9
- CDH10
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| Selectins |
- E-selectin
- L-selectin
- P-selectin
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| Other |
- Lymphocyte homing receptor: CD44
- L-selectin
- integrin (VLA-4, LFA-1)
- Carcinoembryonic antigen
- CD22
- CD24
- CD44
- CD146
- CD164
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- See also
- cell membrane protein disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr
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Histology: Epithelial proteins (TH H1.00.01.1)
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| Lateral/cell-cell |
- Cell adhesion molecules: Adherens junction
- Desmosome
- Ion channels: Gap junction/Connexon
- Cytoskeleton: Desmosome
- Desmoplakin
- Plakoglobin
- Tonofibril
- other membrane proteins: Tight junction
- Claudin
- Occludin
- MARVELD2
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| Basal/cell-matrix |
- Basal lamina
- Hemidesmosome/Tonofibril
- Focal adhesion
- Costamere
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| Apical |
- Cilia/Kinocilium
- Microvilli/Stereocilia (STRC)
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B strc: edmb (perx), skel (ctrs), epit, cili, mito, nucl (chro)
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![Classical [ edit ]](https://1mg.info/0/0/i/2642.jpg)