Ve-ptp Modulates Vascular Integrity by Promoting Adherens Junction Maturation
- Authors
- Carra, S., Foglia, E., Cermenati, S., Bresciani, E., Giampietro, C., Lora Lamia, C., Dejana, E., Beltrame, M., and Cotelli, F.
- ID
- ZDB-PUB-121221-13
- Date
- 2012
- Source
- PLoS One 7(12): e51245 (Journal)
- Registered Authors
- Beltrame, Monica, Cotelli, Franco
- Keywords
- Embryos, Vascular permeability, Zebrafish, Tight junctions, Blood, Endothelial cells, Tails, Junctional complexes
- MeSH Terms
-
- Adherens Junctions/enzymology
- Adherens Junctions/physiology*
- Animals
- Base Sequence
- Blood Vessels/enzymology
- Blood Vessels/physiology*
- Blotting, Western
- Cells, Cultured
- DNA Primers
- Fluorescent Antibody Technique
- Humans
- In Situ Hybridization
- Neovascularization, Physiologic
- Receptor-Like Protein Tyrosine Phosphatases, Class 3/metabolism*
- Reverse Transcriptase Polymerase Chain Reaction
- Zebrafish
- PubMed
- 23251467 Full text @ PLoS One
Background
Endothelial cell junctions control blood vessel permeability. Altered permeability can be associated with vascular fragility that leads to vessel weakness and haemorrhage formation. In vivo studies on the function of genes involved in the maintenance of vascular integrity are essential to better understand the molecular basis of diseases linked to permeability defects. Ve-ptp (Vascular Endothelial-Protein Tyrosine Phosphatase) is a transmembrane protein present at endothelial adherens junctions (AJs).
Methodology/Principal Findings
We investigated the role of Ve-ptp in AJ maturation/stability and in the modulation of endothelial permeability using zebrafish (Danio rerio). Whole-mount in situ hybridizations revealed zve-ptp expression exclusively in the developing vascular system. Generation of altered zve-ptp transcripts, induced separately by two different splicing morpholinos, resulted in permeability defects closely linked to vascular wall fragility. The ultrastructural analysis revealed a statistically significant reduction of junction complexes and the presence of immature AJs in zve-ptp morphants but not in control embryos.
Conclusions/Significance
Here we show the first in vivo evidence of a potentially critical role played by Ve-ptp in AJ maturation, an important event for permeability modulation and for the development of a functional vascular system.