TY - JOUR T1 - The Amot/Integrin protein complex transmits mechanical forces required for vascular expansion JF - bioRxiv DO - 10.1101/2021.01.14.426638 SP - 2021.01.14.426638 AU - Yuanyuan Zhang AU - Yumeng Zhang AU - Sumako Kameishi AU - Giuseppina Barutello AU - Yujuan Zheng AU - Nicholas P. Tobin AU - John Nicosia AU - Katharina Hennig AU - David Kung-Chun Chiu AU - Martial Balland AU - Thomas H. Barker AU - Federica Cavallo AU - Lars Holmgren Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/01/14/2021.01.14.426638.abstract N2 - Vascular development is a complex multistep process involving the coordination of cellular functions such as migration, proliferation and differentiation. Understanding the underlying mechanisms of these processes is of importance due to involvement of vessel expansion in various pathologies. How mechanical forces generated by cells and transmission of these physical forces control vascular development is poorly understood. Using an endothelial-specific genetic model in mice, we show that deletion of the scaffold protein, Angiomotin (Amot), inhibits migration and expansion of physical and pathological vascular network. We further show that Amot is required for tip cell migration and the extension of cellular filopodia. Exploiting in vivo and in vitro molecular approaches, we show that Amot binds talin and is essential for relaying forces between fibronectin and the cytoskeleton. Finally, we provide evidence that Amot is a novel component of the endothelial integrin adhesome and propose that Amot integrates spatial cues from the extra-cellular matrix in order to form a functional vascular network.Competing Interest StatementThe authors have declared no competing interest. ER -