Gagné Valérie, Moreau Julie, Plourde Mélodie, Lapointe Mathieu, Lord Mathieu, Gagnon Edith, Fernandes Maria J G
Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ-CHUL, Department of Anatomy and Physiology, Université Laval, Boul. Laurier, Québec, Québec, Canada.
Cell Motil Cytoskeleton. 2009 Sep;66(9):754-68. doi: 10.1002/cm.20405.
Angiostatin is a potent inhibitor of angiogenesis. One mechanism through which angiostatin inhibits angiogenesis is by binding to the cell surface protein p80-angiomotin. The p80-angiomotin protein promotes angiogenesis, in part, by conferring a hypermigratory phenotype to endothelial cells. Although p80-angiomotin is extensively characterized, less is known about the related protein angiomotin-like 1. We report that angiomotin-like 1 forms part of a protein complex containing p80-angiomotin. Structure-function studies revealed that angiomotin-like 1 associates with this p80-angiomotin-containing complex via its coiled-coil domain. Since p80-angiomotin plays a role in cell migration, a process that involves the remodeling of the actin cytoskeleton, we then addressed the hypothesis that angiomotin-like 1 may interact with the cytoskeleton. Immunofluorescence studies reveal that angiomotin-like 1 not only co-localizes with filamentous actin but also significantly modifies the architecture of the actin cytoskeleton. Regarding migration, angiomotin-like 1 increases the velocity of migration and decreases the persistence of migration directionality. Together these observations strongly suggest that angiomotin-like 1 is involved in actin-cytoskeleton-based processes, in part, via its interaction with a p80-angiomotin-containing complex and the actin cytoskeleton. These findings have important implications for angiogenesis-driven disease since angiomotin and angiomotin-like 1 are both expressed in capillaries.
血管抑素是一种有效的血管生成抑制剂。血管抑素抑制血管生成的一种机制是通过与细胞表面蛋白p80-血管动蛋白结合。p80-血管动蛋白部分地通过赋予内皮细胞高迁移表型来促进血管生成。尽管p80-血管动蛋白已得到广泛研究，但对相关蛋白血管动蛋白样1的了解较少。我们报告血管动蛋白样1是包含p80-血管动蛋白的蛋白复合物的一部分。结构-功能研究表明，血管动蛋白样1通过其卷曲螺旋结构域与这个包含p80-血管动蛋白的复合物缔合。由于p80-血管动蛋白在细胞迁移中起作用，而细胞迁移过程涉及肌动蛋白细胞骨架的重塑，因此我们接着探讨了血管动蛋白样1可能与细胞骨架相互作用的假说。免疫荧光研究表明，血管动蛋白样1不仅与丝状肌动蛋白共定位，而且显著改变肌动蛋白细胞骨架的结构。关于迁移，血管动蛋白样1增加迁移速度并降低迁移方向性的持续性。这些观察结果共同强烈表明，血管动蛋白样1部分地通过与包含p80-血管动蛋白的复合物以及肌动蛋白细胞骨架相互作用而参与基于肌动蛋白细胞骨架的过程。这些发现对血管生成驱动的疾病具有重要意义，因为血管动蛋白和血管动蛋白样1在毛细血管中均有表达。
