Differential roles of p80- and p130-angiomotin in the switch between migration and stabilization of endothelial cells

• Published in: Biochimica et biophysica acta Vol. 1783; no. 3; pp. 429 - 437
• Main Authors: Ernkvist, Mira, Birot, Olivier, Sinha, Indranil, Veitonmaki, Niina, Nyström, Staffan, Aase, Karin, Holmgren, Lars
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.03.2008
• Subjects: Actin; Angiogenesis; Animals; Animals, Newborn; Calcium switch; Cell Adhesion - physiology; Cell Communication - physiology; Cell Movement - physiology; Cells, Cultured; CHO Cells; Cricetinae; Cricetulus; Dimerization; Dogs; Endothelial Cells - metabolism; Endothelial Cells - physiology; Intercellular Signaling Peptides and Proteins - metabolism; Intercellular Signaling Peptides and Proteins - physiology; Medicin och hälsovetenskap; Mice; Microfilament Proteins - metabolism; Microfilament Proteins - physiology; Neovascularization, Physiologic - physiology; Protein Binding; Protein Isoforms - metabolism; Protein Isoforms - physiology; Protein Transport; Retina; Retinal Vessels - growth & development; Retinal Vessels - metabolism; Tight junction; Angiogenesis; Retina; Tight junction; Actin; Calcium switch
• DOI: 10.1016/j.bbamcr.2007.11.018
• ISSN: 0167-4889; 0006-3002

We have previously shown that angiomotin (Amot) plays an important role in growth factor-induced migration of endothelial cells in vitro. Genetic knock-down of Amot in zebrafish also results in inhibition of migration of intersegmental vessels in vivo. Amot is expressed as two different isoforms, p80-Amot and p130-Amot. Here we have analyzed the expression of the two Amot isoforms during retinal angiogenesis in vivo and demonstrate that p80-Amot is expressed during the migratory phase. In contrast, p130-Amot is expressed during the period of blood vessel stabilization and maturation. We also show that the N-terminal domain of p130-Amot serves as a targeting domain responsible for localization of p130-Amot to actin and tight junctions. We further show that the relative expression levels of p80-Amot and p130-Amot regulate a switch between a migratory and a non-migratory cell phenotype where the migratory function of p80-Amot is dominant over the stabilization and maturation function of p130-Amot. Our data indicates that homo-oligomerization of p80-Amot and hetero-oligomerization of both isoforms are critical for this regulation.