Ubiquitination of VE-cadherin regulates inflammation-induced vascular permeability in vivo.
EMBO Rep
; 25(9): 4013-4032, 2024 Sep.
Article
en En
| MEDLINE
| ID: mdl-39112792
ABSTRACT
VE-cadherin is a major component of the cell adhesion machinery which provides integrity and plasticity of the barrier function of endothelial junctions. Here, we analyze whether ubiquitination of VE-cadherin is involved in the regulation of the endothelial barrier in inflammation in vivo. We show that histamine and thrombin stimulate ubiquitination of VE-cadherin in HUVEC, which is completely blocked if the two lysine residues K626 and K633 are replaced by arginine. Similarly, these mutations block histamine-induced endocytosis of VE-cadherin. We describe two knock-in mouse lines with endogenous VE-cadherin being replaced by either a VE-cadherin K626/633R or a VE-cadherin KallR mutant, where all seven lysine residues are mutated. Mutant mice are viable, healthy and fertile with normal expression levels of junctional VE-cadherin. Histamine- or LPS-induced vascular permeability in the skin or lung of both of these mutant mice are clearly and similarly reduced in comparison to WT mice. Additionally, we detect a role of K626/633 for lysosomal targeting. Collectively, our findings identify ubiquitination of VE-cadherin as important for the induction of vascular permeability in the inflamed skin and lung.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Permeabilidad Capilar
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Antígenos CD
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Cadherinas
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Ubiquitinación
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Inflamación
Límite:
Animals
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Humans
Idioma:
En
Año:
2024
Tipo del documento:
Article