Human angiomotin-like 1 associates with an angiomotin protein complex through its coiled-coil domain and induces the remodeling of the actin cytoskeleton

• Published in: Cell motility and the cytoskeleton 2009-09, Vol.66 (9), p.754-768
• Main Authors: Gagné, Valérie, Moreau, Julie, Plourde, Mélodie, Lapointe, Mathieu, Lord, Mathieu, Gagnon, Édith, Fernandes, Maria J. G.
• Format: Article
• Language: English
• Subjects: actin cytoskeleton; Actins - metabolism; angiogenesis; cell migration; Cell Movement - physiology; Cytoskeleton - metabolism; HeLa Cells; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; motins; Neovascularization, Physiologic; protein domains; Protein Structure, Tertiary - genetics; Protein Structure, Tertiary - physiology
• ISSN: 0886-1544; 1097-0169
• 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. Cell Motil. Cytoskeleton 2009. © 2009 Wiley‐Liss, Inc.