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

被引:64
作者
Ernkvist, Mira [1 ]
Birot, Olivier [1 ]
Sinha, Indranil [1 ]
Veitonmaki, Niina [1 ]
Nystrom, Staffan [1 ]
Aase, Karin [1 ]
Holmgren, Lars [1 ]
机构
[1] Karolinska Inst, Canc Ctr Karolinska, Dept Pathol & Oncol, S-17176 Stockholm, Sweden
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2008年 / 1783卷 / 03期
关键词
actin; angiogenesis; calcium switch; retina; tight junction;
D O I
10.1016/j.bbamcr.2007.11.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:429 / 437
页数:9
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