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.

中文翻译：

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Amot /整合素蛋白复合物传递血管扩张所需的机械力

血管发育是一个复杂的多步骤过程，涉及细胞功能的协调，例如迁移，增殖和分化。由于血管扩张涉及多种病理，因此了解这些过程的潜在机制非常重要。由细胞产生的机械力以及这些物理力的传递如何控制血管发育的了解很少。使用小鼠中的内皮特异性遗传模型，我们表明删除支架蛋白，血管动蛋白（Amot），抑制迁移和物理和病理血管网络的扩张。我们进一步表明，Amot是尖端细胞迁移和细胞丝状伪足扩展所必需的。利用体内和体外分子方法，我们表明，Amot结合塔林蛋白，是纤连蛋白和细胞骨架之间传递力必不可少的。最后，我们提供证据表明Amot是内皮整联蛋白胶体的新成分，并提出Amot整合了细胞外基质的空间线索以形成功能性血管网络。