RT Journal Article
SR Electronic
T1 The Amot/Integrin protein complex transmits mechanical forces required for vascular expansion
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.14.426638
DO 10.1101/2021.01.14.426638
A1 Yuanyuan Zhang
A1 Yumeng Zhang
A1 Sumako Kameishi
A1 Giuseppina Barutello
A1 Yujuan Zheng
A1 Nicholas P. Tobin
A1 John Nicosia
A1 Katharina Hennig
A1 David Kung-Chun Chiu
A1 Martial Balland
A1 Thomas H. Barker
A1 Federica Cavallo
A1 Lars Holmgren
YR 2021
UL http://biorxiv.org/content/early/2021/01/14/2021.01.14.426638.abstract
AB 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.