Differential roles of p80- and p130-angiomotin in the switch between migration and stabilization of endothelial cells.
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.
Ernkvist
Mira
M
Cancer Centrum Karolinska, Department of Oncology and Pathology, Karolinska Institutet, CCK R8:03, 171 76 Stockholm, Sweden.
Birot
Olivier
O
Sinha
Indranil
I
Veitonmaki
Niina
N
Nyström
Staffan
S
Aase
Karin
K
Holmgren
Lars
L
D000091082:Angiomotins; D000818:Animals; D000831:Animals, Newborn; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D019281:Dimerization; D004285:Dogs; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011485:Protein Binding; D020033:Protein Isoforms / Q000378:metabolism / Q000502:physiology; D021381:Protein Transport; D012171:Retinal Vessels / Q000254:growth & development / Q000378:metabolism
C511047:Amot protein, mouse; D000091082:Angiomotins; D036341:Intercellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D020033:Protein Isoforms