Cadherin-5, or VE-cadherin (vascular endothelial cadherin), also known as CD144 (Cluster of Differentiation 144), is a type of cadherin. It is encoded by the human gene CDH5.[5]
Function
editVE-cadherin is a classical cadherin from the cadherin superfamily and the gene is located in a six-cadherin cluster in a region on the long arm of chromosome 16 that is involved in loss of heterozygosity events in breast and prostate cancer. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Functioning as a classic cadherin by imparting to cells the ability to adhere in a homophilic manner, the protein may play an important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions.[6]
Integrity of intercellular junctions is a major determinant of permeability of the endothelium, and the VE-cadherin-based adherens junction is thought to be particularly important. VE-cadherin is known to be required for maintaining a restrictive endothelial barrier – early studies using blocking antibodies to VE-cadherin increased monolayer permeability in cultured cells[7] and resulted in interstitial edema and hemorrhage in vivo.[8] A recent study has shown that TNFAIP3 (A20, a dual-ubiquitin editing enzyme) is essential for stability and expression of VE-cadherin. Deubiquitinase function of A20 was shown to remove ubiquitin chains from VE-cadherin, thereby prevented loss of VE-cadherin expression at the endothelial adherens junctions.[9]
VE-cadherin is indispensable for proper vascular development – there have been two transgenic mouse models of VE-cadherin deficiency, both embryonic lethal due to vascular defects.[10][11] Further studies using one of these models revealed that although vasculogenesis occurred, nascent vessels collapsed or disassembled in the absence of VE-cadherin.[12] Therefore, it was concluded that VE-cadherin serves the purpose of maintaining newly formed vessels.
Interactions
editVE-cadherin has been shown to interact with:
As a biomarker
editVE-cadherin may serve as a biomarker for radiation exposure.[20]
See also
editReferences
editFurther reading
edit- Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, Ruco LP, Dejana E (1992). "A novel endothelial-specific membrane protein is a marker of cell-cell contacts". J. Cell Biol. 118 (6): 1511–22. doi:10.1083/jcb.118.6.1511. PMC 2289607. PMID 1522121.
- Suzuki S, Sano K, Tanihara H (1991). "Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue". Cell Regul. 2 (4): 261–70. doi:10.1091/mbc.2.4.261. PMC 361775. PMID 2059658.
- Breviario F, Caveda L, Corada M, Martin-Padura I, Navarro P, Golay J, Introna M, Gulino D, Lampugnani MG, Dejana E (1995). "Functional properties of human vascular endothelial cadherin (7B4/cadherin-5), an endothelium-specific cadherin". Arterioscler. Thromb. Vasc. Biol. 15 (8): 1229–39. doi:10.1161/01.ATV.15.8.1229. PMID 7627717.
- Ali J, Liao F, Martens E, Muller WA (1997). "Vascular endothelial cadherin (VE-cadherin): cloning and role in endothelial cell-cell adhesion". Microcirculation. 4 (2): 267–77. doi:10.3109/10739689709146790. PMID 9219219. S2CID 21501093.
- Lampugnani MG, Corada M, Andriopoulou P, Esser S, Risau W, Dejana E (1997). "Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells". J. Cell Sci. 110 (17): 2065–77. doi:10.1242/jcs.110.17.2065. PMID 9378757.
- Lewalle JM, Bajou K, Desreux J, Mareel M, Dejana E, Noël A, Foidart JM (1998). "Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro". Exp. Cell Res. 237 (2): 347–56. doi:10.1006/excr.1997.3799. hdl:2268/61990. PMID 9434630.
- Kremmidiotis G, Baker E, Crawford J, Eyre HJ, Nahmias J, Callen DF (1998). "Localization of human cadherin genes to chromosome regions exhibiting cancer-related loss of heterozygosity". Genomics. 49 (3): 467–71. doi:10.1006/geno.1998.5281. PMID 9615235.
- Kowalczyk AP, Navarro P, Dejana E, Bornslaeger EA, Green KJ, Kopp DS, Borgwardt JE (1998). "VE-cadherin and desmoplakin are assembled into dermal microvascular endothelial intercellular junctions: a pivotal role for plakoglobin in the recruitment of desmoplakin to intercellular junctions". J. Cell Sci. 111 (20): 3045–57. doi:10.1242/jcs.111.20.3045. PMID 9739078.
- Kawashima M, Kitagawa M (1999). "An immunohistochemical study of cadherin 5 (VE-cadherin) in vascular endothelial cells in placentas with gestosis". J. Obstet. Gynaecol. Res. 24 (6): 375–84. doi:10.1111/j.1447-0756.1998.tb00112.x. PMID 10063232. S2CID 12405995.
- Carmeliet P, Lampugnani MG, Moons L, Breviario F, Compernolle V, Bono F, Balconi G, Spagnuolo R, Oosthuyse B, Dewerchin M, Zanetti A, Angellilo A, Mattot V, Nuyens D, Lutgens E, Clotman F, de Ruiter MC, Gittenberger-de Groot A, Poelmann R, Lupu F, Herbert JM, Collen D, Dejana E (1999). "Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis". Cell. 98 (2): 147–57. doi:10.1016/S0092-8674(00)81010-7. PMID 10428027. S2CID 2668221.
- Ukropec JA, Hollinger MK, Salva SM, Woolkalis MJ (2000). "SHP2 association with VE-cadherin complexes in human endothelial cells is regulated by thrombin". J. Biol. Chem. 275 (8): 5983–6. doi:10.1074/jbc.275.8.5983. PMID 10681592.
- Shimoyama Y, Tsujimoto G, Kitajima M, Natori M (2001). "Identification of three human type-II classic cadherins and frequent heterophilic interactions between different subclasses of type-II classic cadherins". Biochem. J. 349 (Pt 1): 159–67. doi:10.1042/0264-6021:3490159. PMC 1221133. PMID 10861224.
- Shaw SK, Bamba PS, Perkins BN, Luscinskas FW (2001). "Real-time imaging of vascular endothelial-cadherin during leukocyte transmigration across endothelium". J. Immunol. 167 (4): 2323–30. doi:10.4049/jimmunol.167.4.2323. PMID 11490021.
- van Buul JD, Voermans C, van den Berg V, Anthony EC, Mul FP, van Wetering S, van der Schoot CE, Hordijk PL (2002). "Migration of human hematopoietic progenitor cells across bone marrow endothelium is regulated by vascular endothelial cadherin". J. Immunol. 168 (2): 588–96. doi:10.4049/jimmunol.168.2.588. PMID 11777950.
- Ferber A, Yaen C, Sarmiento E, Martinez J (2002). "An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation". Exp. Cell Res. 274 (1): 35–44. doi:10.1006/excr.2001.5436. PMID 11855855.
- Gorlatov S, Medved L (2002). "Interaction of fibrin(ogen) with the endothelial cell receptor VE-cadherin: mapping of the receptor-binding site in the NH2-terminal portions of the fibrin beta chains". Biochemistry. 41 (12): 4107–16. doi:10.1021/bi0160314. PMID 11900554.
- Di Simone N, Castellani R, Caliandro D, Caruso A (2003). "Antiphospholid antibodies regulate the expression of trophoblast cell adhesion molecules". Fertil. Steril. 77 (4): 805–11. doi:10.1016/S0015-0282(01)03258-7. PMID 11937138.
- Zanetti A, Lampugnani MG, Balconi G, Breviario F, Corada M, Lanfrancone L, Dejana E (2002). "Vascular endothelial growth factor induces SHC association with vascular endothelial cadherin: a potential feedback mechanism to control vascular endothelial growth factor receptor-2 signaling". Arterioscler. Thromb. Vasc. Biol. 22 (4): 617–22. doi:10.1161/01.ATV.0000012268.84961.AD. PMID 11950700.
- Lampugnani MG, Zanetti A, Breviario F, Balconi G, Orsenigo F, Corada M, Spagnuolo R, Betson M, Braga V, Dejana E (2002). "VE-cadherin regulates endothelial actin activating Rac and increasing membrane association of Tiam". Mol. Biol. Cell. 13 (4): 1175–89. doi:10.1091/mbc.01-07-0368. PMC 102260. PMID 11950930.
- Vincent PA, Xiao K, Buckley KM, Kowalczyk AP (2004). "VE-cadherin: adhesion at arm's length". Am J Physiol Cell Physiol. 286 (5): C987–97. doi:10.1152/ajpcell.00522.2003. PMID 15075197.
External links
edit- VE-cadherin+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- CDH5 human gene location in the UCSC Genome Browser.
- CDH5 human gene details in the UCSC Genome Browser.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.