Cadherin 5, type 2 or VE-cadherin (vascular endothelial cadherin) also known as CD144 (Cluster of Differentiation144), is a type of cadherin. It is encoded by the human geneCDH5.[1]
VE-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.[2]
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[3] and resulted in interstitial edema and hemorrhage in vivo.[4] A recent study has shown that A20 (which is 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. [5]
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.[6][7] Further studies using one of these models revealed that although vasculogenesis occurred, nascent vessels collapsed or disassembled in the absence of VE-cadherin.[8] Therefore, it was concluded that VE-cadherin serves the purpose of maintaining newly formed vessels.
↑Corada M, Liao F, Lindgren M, Lampugnani MG, Breviario F, Frank R, Muller WA, Hicklin DJ, Bohlen P, Dejana E (March 2001). "Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability". Blood. 97 (6): 1679–84. doi:10.1182/blood.V97.6.1679. PMID11238107.
↑Corada M, Zanetta L, Orsenigo F, Breviario F, Lampugnani MG, Bernasconi S, Liao F, Hicklin DJ, Bohlen P, Dejana E (August 2002). "A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability". Blood. 100 (3): 905–11. doi:10.1182/blood.V100.3.905. PMID12130501.
↑Soni D, Wang DM, Regmi SC, Mittal M, Vogel SM, Schlüter D, Tiruppathi C (May 2018). "Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury". Cell Death Discovery. 4 (60). doi:10.1038/s41420-018-0056-3.
↑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 (July 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. PMID10428027.
↑Crosby CV, Fleming PA, Argraves WS, Corada M, Zanetta L, Dejana E, Drake CJ (April 2005). "VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly". Blood. 105 (7): 2771–6. doi:10.1182/blood-2004-06-2244. PMID15604224.
↑ 9.09.19.2Lewalle JM, Bajou K, Desreux J, Mareel M, Dejana E, Noël A, Foidart JM (Dec 1997). "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. PMID9434630.
↑Ferber A, Yaen C, Sarmiento E, Martinez J (Mar 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. PMID11855855.
↑Lampugnani MG, Corada M, Andriopoulou P, Esser S, Risau W, Dejana E (Sep 1997). "Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells". J. Cell Sci. 110 (17): 2065–77. PMID9378757.
↑Besco JA, Hooft van Huijsduijnen R, Frostholm A, Rotter A (2006). "Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Res. 1116 (1): 50–7. doi:10.1016/j.brainres.2006.07.122. PMID16973135.
↑Hérodin F, Voir D, Vilgrain I, Courçon M, Drouet M, Boittin FX (June 2016). "Soluble Vascular Endothelial Cadherin as a New Biomarker of Irradiation in Highly Irradiated Baboons with Bone Marrow Protection". Health Physics. 110 (6): 598605. doi:10.1097/HP.0000000000000481. PMID27115227.
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. PMID7627717.
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. PMID9219219.
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. PMID9378757.
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. PMID9434630.
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. PMID9615235.
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. PMID9739078.
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. PMID10063232.
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. PMID10428027.
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. PMID10681592.
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. PMID11490021.
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. PMID11777950.
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. PMID11855855.
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. PMID11900554.
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. PMID11937138.
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. PMID11950700.
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. PMID15075197.