Abstract
Endothelial cells (ECs) form a monolayer that serves as a barrier between the blood and the underlying tissue. ECs tightly regulate their cell-cell junctions, controlling the passage of soluble materials and immune cells across the monolayer barrier. We studied the role of N-WASP, a key regulator of Arp2/3 complex and actin assembly, in EC monolayers. We report that N-WASP regulates endothelial monolayer integrity by affecting the organization of cell junctions. Depletion of N-WASP resulted in an increase in transendothelial electrical resistance, a measure of monolayer integrity. N-WASP depletion increased the width of cell-cell junctions and altered the organization of F-actin and VE-cadherin at junctions. N-WASP was not present at cell-cell junctions in monolayers under resting conditions, but it was recruited following treatment with sphingosine-1-phosphate. Taken together, our results reveal a novel role for N-WASP in remodeling EC junctions, which is critical for monolayer integrity and function.
Highlights
Endothelial cells line blood vessels, forming a monolayer that acts as a regulated barrier
Depletion of N-WASP Enhances the Integrity of the Endothelial Barrier—To determine whether N-WASP plays a role in endothelial monolayer formation and barrier integrity, we depleted N-WASP from human dermal microvascular endothelial cells in monolayers and measured Transendothelial resistance (TER)
N-WASP depletion caused TER values to increase for endothelial monolayers treated with TNF-␣ as a mimic of inflammatory conditions; this effect was rescued by N-WASP expression (Fig. 1C)
Summary
Endothelial cells line blood vessels, forming a monolayer that acts as a regulated barrier. Results: Endothelial N-WASP organizes VE-cadherin and actin at cellular junctions, which alters barrier integrity. Conclusion: N-WASP regulates monolayer integrity by remodeling cell-cell contacts. Significance: Our results show how endothelial cells use one actin regulator to modulate the endothelial barrier. Endothelial cells (ECs) form a monolayer that serves as a barrier between the blood and the underlying tissue. We report that N-WASP regulates endothelial monolayer integrity by affecting the organization of cell junctions. N-WASP depletion increased the width of cell-cell junctions and altered the organization of F-actin and VE-cadherin at junctions. We report that N-WASP is involved in endothelial monolayer integrity and in proper organization of actin and VE-cadherin at cell-cell junctions. We propose that N-WASP coordinates actin with endothelial junctions to regulate endothelial monolayer integrity
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