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.

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

Zhang Y.
First
;
Barutello G.;Cavallo F.;
2021-01-01

Abstract

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.
2021
36
8
109616
109651
adhesome; angiogenesis; endothelial; force; integrin; mechanotransduction; migration; talin; tumor; vascular; Angiomotins; Animals; Cell Membrane; Cell Movement; Cytoskeleton; Endothelium; Fibronectins; Integrins; Mice, Transgenic; Neovascularization, Physiologic; Plasma Substitutes; Pseudopodia
Zhang Y.; Zhang Y.; Kameishi S.; Barutello G.; Zheng Y.; Tobin N.P.; Nicosia J.; Hennig K.; Chiu D.K.-C.; Balland M.; Barker T.H.; Cavallo F.; Holmgren L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1849491
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