Cadherin-5, 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.[5]
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.[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.
^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. doi:10.1242/jcs.110.17.2065. 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. S2CID23343123.
^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): 598–605. doi:10.1097/HP.0000000000000481. PMID27115227. S2CID3314728.
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. S2CID21501093.
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. 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. hdl:2268/61990. 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. doi:10.1242/jcs.111.20.3045. 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. S2CID12405995.
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.
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.