CDH5
Description
The CDH5 (cadherin 5) is a protein-coding gene located on chromosome 16.
Cadherin-5, also known as VE-cadherin (vascular endothelial cadherin) or CD144, is a type of cadherin encoded by the human gene CDH5. It is a classical cadherin from the cadherin superfamily, located in a six-cadherin cluster on chromosome 16. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein with five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail. It functions as a classic cadherin, enabling cells to adhere in a homophilic manner. This protein may play a crucial role in endothelial cell biology by controlling the cohesion and organization of intercellular junctions. The integrity of these junctions significantly influences the permeability of the endothelium, with the VE-cadherin-based adherens junction considered particularly important. VE-cadherin is essential for maintaining a restrictive endothelial barrier. Early studies using blocking antibodies to VE-cadherin demonstrated increased monolayer permeability in cultured cells and led to interstitial edema and hemorrhage in vivo. Recent research has shown that TNFAIP3 (A20), a dual-ubiquitin editing enzyme, is vital for the stability and expression of VE-cadherin. A20's deubiquitinase function removes ubiquitin chains from VE-cadherin, preventing its loss at the endothelial adherens junctions. VE-cadherin is indispensable for proper vascular development. Two transgenic mouse models with VE-cadherin deficiency have been created, both exhibiting embryonic lethality due to vascular defects.
Cadherins are calcium-dependent cell adhesion proteins that preferentially interact with themselves in a homophilic manner, contributing to the sorting of different cell types. This cadherin plays a significant role in endothelial cell biology by regulating the cohesion and organization of intercellular junctions. It associates with alpha-catenin, forming a link to the cytoskeleton. Working in conjunction with KRIT1 and PALS1, it establishes and maintains proper endothelial cell polarity and vascular lumen formation. These effects are mediated by the recruitment and activation of the Par polarity complex and RAP1B. It is essential for the activation of PRKCZ and the localization of phosphorylated PRKCZ, PARD3, TIAM1 and RAP1B to the cell junction.
CDH5 is also known as 7B4, CD144.
