Cadherin-5, or VE-cadherin (vascular endothelial cadherin), also known as CD144 (
Cluster of Differentiation 144), is a type of
cadherin
Cadherins (named for "calcium-dependent adhesion") are cell adhesion molecules important in forming adherens junctions that let cells adhere to each other. Cadherins are a class of type-1 transmembrane proteins, and they depend on calcium (Ca2+) ...
. It is encoded by the human
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
''CDH5''.
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
Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
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
The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the r ...
, 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
Ubiquitin is a small (8.6 kDa) regulatory protein found in most tissues of eukaryotic organisms, i.e., it is found ''ubiquitously''. It was discovered in 1975 by Gideon Goldstein and further characterized throughout the late 1970s and 19 ...
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
Vasculogenesis is the process of blood vessel formation, occurring by a ''De novo synthesis, de novo'' production of endothelial cells. It is the first stage of the formation of the vascular network, closely followed by angiogenesis.
Process
...
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
Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcrip ...
*
Plakoglobin[
* PTPRB]Catenin (cadherin-associated protein), alpha 1
αE-catenin, also known as Catenin alpha-1 is a protein that in humans is encoded by the ''CTNNA1'' gene. αE-catenin is highly expressed in cardiac muscle and localizes to adherens junctions at intercalated disc structures where it functions t ...
[
* ]CTNND1
p120 catenin, or simply p120, also called catenin delta-1, is a protein that in humans is encoded by the ''CTNND1'' gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a se ...
As a biomarker
VE-cadherin may serve as a biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...
for radiation exposure.
See also
* Vasculogenic Mimicry
References
Further reading
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External links
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{{Cell adhesion molecules
Clusters of differentiation
Biomarkers