Vinculin strengthens the endothelial barrier during vascular development

Abstract

Remodelling of cell-cell junctions is crucial for proper tissue development and barrier function. The Cadherin-based adherens junctions anchor via β-Catenin and α-Catenin to the actomyosin cytoskeleton, together forming a junctional mechanotransduction complex. Tension-induced conformational changes in the mechanosensitive α-Catenin protein induce junctional Vinculin recruitment. In endothelial cells, Vinculin protects the remodelling VE-Cadherin junctions. In this study, we have addressed the role of Vinculin in endothelial barrier function in the developing vasculature. In vitro experiments, using endothelial cells in which α-Catenin was replaced by a Vinculin-binding deficient mutant, showed that junctional recruitment of Vinculin promotes endothelial barrier function. To assess the role of Vinculin within blood vessels in vivo, we next investigated barrier function in the vasculature of Vinculin knockout zebrafish. In the absence of Vinculin, sprouting angiogenesis and vessel perfusion still occurred. Intriguingly, the absence of Vinculin made the blood vessels more permeable for 10 kDa dextran molecules, but not for larger tracers. Taken together, our findings demonstrate that Vinculin strengthens the endothelial barrier and prevents vascular leakage in developing vessels.

Interplay of actin nematodynamics and anisotropic tension controls endothelial mechanics

“…As such, the cellular dynamics we report here could underlie vessel remodeling and pathological mechanoadaptation of vessels. Tension-induced remodeling of adherens junctions is evident by shape change and actin and vinculin association, a mechanism previously linked to the protection of tissue integrity and barrier function Millán et al (2010); Huveneers et al (2012); Stoel et al (2023); Oldenburg and Rooij (2014). In vivo, an increase in luminal pressure has been reported to trigger vessel radial growth and junction remodeling along the tension direction in the zebrafish, mirroring our observations Kotini et al (2022).…”

Focal Adhesion’s Role in Cardiomyocytes Function: From Cardiomyogenesis to Mechanotransduction

“…Interestingly, in the presence of a specific mutant vinculin that is unable to bind to other ligands such as the Arp2/3 complex, the vinculin mutant disrupts actin binding and reduces the ability of cells to spread, adhere, and sustain traction forces [101,108]. All these molecular mechanisms of mechanotransduction have been underlined and confirmed by several in vivo studies [39,42,[109][110][111][112][113][114].…”

Influence of PHA Substrate Surface Characteristics on the Functional State of Endothelial Cells

“…In the present study, the participation of this protein in maintaining the endothelial barrier during changes dictated by the cytoskeleton in mechanochemical interactions with polymer samples with different surface profiles is considered [ 87 , 88 , 89 ]. Data from Stephan Huveneers [ 90 ] show that there is a vinculin-dependent mechanosensory interaction between cadherins that mediates adequate remodeling of endothelial junctions to promote, for example, transendothelial migration of leukocytes to the site of injury or infection to reduce the inflammatory response. Thus, when studying intercellular contacts, it can be noted that the maximum number of vinculin binding sites is observed on the P3HB3HHx sample at the points of contact between the lamellipodia of neighboring cells.…”