Stephan Huveneers - University of Amsterdam

Le 15 November 2022

Amphi Denis Escande

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15h30

Junctional mechanotransduction in angiogenesis

Junctional mechanotransduction in angiogenesis

Dr Stephan Huveneers, MD, PhD
Amsterdam UMC - University of Amsterdam
Associate Professor

Abstract

Angiogenic sprouting depends on collective migration and coordinated rearrangements of endothelial leader and follower cells. VE-cadherin-based adherens junctions have emerged as key cell-cell contacts that transmit forces between endothelial cells and trigger signals during collective cell migration in angiogenesis. Previously, we have described dedicated molecular events that occur at VE-cadherin-based junctions during their force-dependent remodeling. These findings shed light on the role of cytoskeletal adapter proteins such as Vinculin and the membrane curvature-sensing BAR proteins in endothelial cell dynamics. Using live cell microscopy we unraveled how such molecular signals guide the endothelial cells during collective migration and angiogenesis. Our recent findings substantiate the importance of Vinculin in strengthening of the endothelial barrier during vascular development. Moreover, we find that tensional forces propagate directional cues by polarized VE-cadherin trafficking to guide vascular development via the recruitment of different BAR proteins. Together these results show that there are tailored mechanotransduction responses at the endothelial junctions to finely tune the endothelium.

Biography

Dr. Stephan Huveneers is Associate Professor of the Vascular Microenvironment and Integrity lab at Amsterdam UMC, University of Amsterdam. His group investigates the role of molecular events that take place at endothelial adhesions within the context of the blood vessel wall. The response of the vascular endothelium to mechanical forces is a research area that is only at the start of its elucidation. Failure to respond to forces has direct consequences for blood vessel development and barrier function and underlies stiffness-related cardiovascular disease. The Huveneers lab studies the molecular and cellular mechanisms that are responsible for endothelial mechanotransduction responses through cell adhesion. Our recent studies have resulted in the identification and unraveling of at least two novel molecular systems in stiffness-related vascular function: these findings place DLC1 as a crucial and prominent direct target of the mechanotransducers YAP/TAZ in angiogenesis (van der Stoel et al, Journal of Cell Science 2020) and vascular inflammation (Schimmel et al, Cell Reports 2018). In addition, we discovered a novel force-dependent Pacsin2-EHD4 junction complex which controls trafficking of VE-cadherin for endothelial barrier function and guides new vessels during angiogenesis (Dorland, Malinova et al Nature Communications 2016, Malinova & Huveneers, Trends Cell Biol, 2018 and Malinova, Angulo-Urarte et al, Nature Communications 2021).

Mis à jour le 26 June 2023.