Human angiomotin-like 1 associates with an angiomotin protein complex through its coiled-coil domain and induces the remodeling of the actin cytoskeleton.
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.
Gagné
Valérie
V
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.
Moreau
Julie
J
Plourde
Mélodie
M
Lapointe
Mathieu
M
Lord
Mathieu
M
Gagnon
Edith
E
Fernandes
Maria J G
MJ
D000199:Actins / Q000378:metabolism*; D000091082:Angiomotins; D002465:Cell Movement / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins; D018919:Neovascularization, Physiologic; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology
C423985:AMOT protein, human; C510063:AMOTL1 protein, human; D000199:Actins; D000091082:Angiomotins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins