Vinculin strengthens the endothelial barrier during vascular development

Area of Science:

• Cell Biology
• Developmental Biology
• Biophysics

Background:

• Cell-cell junction remodeling is vital for tissue development and barrier integrity.
• Adherens junctions, mediated by cadherins, link to the cytoskeleton via catenins, forming mechanotransduction complexes.
• Vinculin recruitment to junctions is tension-induced and protects endothelial VE-cadherin junctions.

Purpose of the Study:

• To investigate the role of vinculin in endothelial barrier function during vascular development.
• To determine how vinculin influences junctional stability and vascular permeability in vivo and in vitro.

Main Methods:

• In vitro studies using endothelial cells with a vinculin-binding-deficient α-catenin mutant.
• In vivo experiments assessing vascular barrier function in vinculin (vcl) knockout zebrafish.
• Permeability assays using dextran molecules of varying sizes (10 kDa and larger).

Main Results:

• In vitro, vinculin recruitment to junctions enhanced endothelial barrier function.
• In vinculin-deficient zebrafish, angiogenesis and perfusion were normal.
• Absence of vinculin led to increased permeability to 10 kDa dextran but not larger tracers, indicating specific barrier defects.

Conclusions:

• Vinculin plays a crucial role in strengthening the endothelial barrier in developing vasculature.
• Vinculin prevents vascular leakage, particularly for smaller molecules, by stabilizing cell-cell junctions.