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Mechanisms of VE-cadherin processing and degradation in microvascular endothelial cells.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2003 May 23; Vol. 278 (21), pp. 19199-208. Date of Electronic Publication: 2003 Mar 06. - Publication Year :
- 2003
-
Abstract
- VE-cadherin is an endothelial-specific cadherin that plays important roles in vascular morphogenesis and growth control. To investigate the mechanisms by which endothelial cells regulate cadherin cell surface levels, a VE-cadherin mutant containing the non-adhesive interleukin-2 (IL-2) receptor extracellular domain and the VE-cadherin cytoplasmic tail (IL-2R-VE-cadcyto) was expressed in microvascular endothelial cells. Expression of the IL-2R-VE-cadcyto mutant resulted in the internalization of endogenous VE-cadherin and in a dramatic decrease in endogenous VE-cadherin levels. The internalized VE-cadherin co-localized with early endosomes, and the lysosomal inhibitor chloroquine dramatically inhibited the down-regulation of VE-cadherin in cells expressing the IL-2R-VE-cadcyto mutant. Chloroquine treatment also resulted in the accumulation of a VE-cadherin fragment lacking the beta-catenin binding domain of the VE-cadherin cytoplasmic tail. The formation of the VE-cadherin fragment could be prevented by treating endothelial cells with proteasome inhibitors. Furthermore, inhibition of the proteasome prevented VE-cadherin internalization and inhibited the disruption of endothelial intercellular junctions by the IL-2RVE-cadcyto mutant. These results provide new insights into the mechanisms of VE-cadherin processing and degradation in microvascular endothelial cells.
- Subjects :
- Adenoviridae genetics
Animals
Antigens, CD
Blotting, Western
COS Cells
Cadherins genetics
Cell Line
Cells, Cultured
Chloroquine pharmacology
Cysteine Endopeptidases
Endosomes metabolism
Fluorescent Antibody Technique
Gene Deletion
Gene Expression
Genetic Vectors
Humans
Intercellular Junctions drug effects
Kidney
Lysosomes drug effects
Lysosomes metabolism
Male
Microcirculation
Multienzyme Complexes antagonists & inhibitors
Mutagenesis
Proteasome Endopeptidase Complex
Receptors, Interleukin-2 genetics
Recombinant Fusion Proteins
Recombinant Proteins
Skin blood supply
Transfection
Cadherins metabolism
Endothelium, Vascular metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 278
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12626512
- Full Text :
- https://doi.org/10.1074/jbc.M211746200