VE-cadherin

Function

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.

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 and resulted in interstitial edema and hemorrhage in vivo. 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.

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. Further studies using one of these models revealed that although vasculogenesis occurred, nascent vessels collapsed or disassembled in the absence of VE-cadherin. Therefore, it was concluded that VE-cadherin serves the purpose of maintaining newly formed vessels.

Interactions

VE-cadherin has been shown to interact with:

• Beta-catenin
• Plakoglobin
• PTPRB
• Catenin (cadherin-associated protein), alpha 1
• CTNND1
• PTPmu (PTPRM)
• PTPrho (PTPRT)

As a biomarker

VE-cadherin may serve as a biomarker for radiation exposure.

References

References

1. (April 1991). "Diversity of the cadherin family: evidence for eight new cadherins in nervous tissue". Cell Regul..
2. "Entrez Gene: CDH5 cadherin 5, type 2, VE-cadherin (vascular epithelium)".
3. (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.
4. (August 2002). "A monoclonal antibody to vascular endothelial-cadherin inhibits tumor angiogenesis without side effects on endothelial permeability". Blood.
5. (May 2018). "Deubiquitinase function of A20 maintains and repairs endothelial barrier after lung vascular injury". Cell Death Discovery.
6. (July 1999). "Targeted deficiency or cytosolic truncation of the VE-cadherin gene in mice impairs VEGF-mediated endothelial survival and angiogenesis". Cell.
7. (May 1999). "Role of vascular endothelial-cadherin in vascular morphogenesis". Development.
8. (April 2005). "VE-cadherin is not required for the formation of nascent blood vessels but acts to prevent their disassembly". Blood.
9. (Dec 1997). "Alteration of interendothelial adherens junctions following tumor cell-endothelial cell interaction in vitro". Exp. Cell Res..
10. (Jun 2002). "Histamine stimulates phosphorylation of adherens junction proteins and alters their link to vimentin". Am. J. Physiol. Lung Cell Mol. Physiol..
11. (Sep 2002). "VE-PTP and VE-cadherin ectodomains interact to facilitate regulation of phosphorylation and cell contacts". EMBO J..
12. (Mar 2002). "An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation". Exp. Cell Res..
13. (Sep 1997). "Cell confluence regulates tyrosine phosphorylation of adherens junction components in endothelial cells". J. Cell Sci..
14. (2005). "Receptor protein tyrosine phosphatase micro regulates the paracellular pathway in human lung microvascular endothelia.". Am J Pathol.
15. (2006). "Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT).". Brain Res.
16. (June 2016). "Soluble Vascular Endothelial Cadherin as a New Biomarker of Irradiation in Highly Irradiated Baboons with Bone Marrow Protection". Health Physics.