Differential roles of p80-and p130-angiomotin in the switch between migration and stabilization of endothelial cells
Differential roles of p80-and p130-angiomotin in the switch between migration and stabilization of endothelial cells
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DOI：
10.1016/j.bbamcr.2007.11.018
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发表时间：
2008-03-01
影响因子：
5.1
通讯作者：
Holmgren, Lars
中科院分区：
文献类型：
--
作者：
Ernkvist, Mira;Birot, Olivier;Holmgren, Lars
我们以前已经表明，血管动蛋白（Amot）在体外生长因子诱导的内皮细胞迁移中起着重要作用。在斑马鱼中基因敲低Amot也导致体内节间血管迁移的抑制。Amot表达为两种不同的同种型，p80-Amot和p130-Amot。在这里，我们分析了两个Amot亚型在体内视网膜血管生成过程中的表达，并证明p80-Amot在迁移期表达。相反，p130-Amot在血管稳定和成熟期间表达。我们还表明，N-末端结构域的p130-Amot作为一个靶向结构域负责本地化的p130-Amot肌动蛋白和紧密连接。我们进一步表明，p80-Amot和p130-Amot的相对表达水平调节迁移和非迁移细胞表型之间的转换，其中p80-Amot的迁移功能主导于p130-Amot的稳定和成熟功能。我们的数据表明，同源寡聚化的p80-Amot和异源寡聚化的两种亚型是至关重要的，这种调节。(c)2007 Elsevier B. V.保留所有权利。
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.