The Amot/integrin protein complex transmits mechanical forces required for vascular expansion

Cell Reports

Thomas H. Barker¹  Giuseppina Barutello²  Federica Cavallo²  David Kung-Chun Chiu³  Yumeng Zhang³  Nicholas P. Tobin³  Sumako Kameishi³  Yuanyuan Zhang³  Yujuan Zheng³  Lars Holmgren³  Katharina Hennig⁴  Martial Balland⁴  John Nicosia⁵ 

[1] Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22904, USA;Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center, University of Turin, Turin 10126, Italy;Department of Oncology-Pathology, Bioclinicum, Karolinska Institutet, Stockholm 17164, Sweden;Laboratoire Interdisciplinaire de Physique, Université Joseph Fourier (Grenoble 1), Saint Martin d’Hères Cedex, 38402, France;Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA;

关键词: angiogenesis;    integrin;    mechanotransduction;    migration;    endothelial;    force;   

DOI  :  

来源: DOAJ

【 摘 要 】

Summary: Vascular development is a complex multistep process involving the coordination of cellular functions such as migration, proliferation, and differentiation. 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 the physiological 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 an important component of the endothelial integrin adhesome and propose that Amot integrates spatial cues from the extracellular matrix to form a functional vascular network.

【 授权许可】

Unknown