Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor
Localization of nectin-free afadin at the leading edge and its involvement in directional cell movement induced by platelet-derived growth factor
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DOI：
10.1242/jcs.048439
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发表时间：
2009-12-01
影响因子：
4
通讯作者：
Takai, Yoshimi
中科院分区：
文献类型：
--
作者：
Miyata, Muneaki;Ogita, Hisakazu;Takai, Yoshimi
Afadin是一种肌动蛋白丝结合蛋白，与免疫球蛋白样细胞间粘附分子nectin结合，在粘附连接的形成中起重要作用。在这里，我们表明，afadin，这并没有绑定到连接素，并定位在运动细胞的前沿，有另一个作用：增强的方向，但不是随机的，细胞运动。当用血小板衍生生长因子（PDGF）刺激NIH 3 T3细胞时，afadin与PDGF受体、α v β 3整合素和nectin样分子-5共定位于前缘，并促进前缘结构的形成和在PDGF刺激方向上的定向细胞运动。然而，这些表型显着干扰敲除afadin，并依赖于结合的afadin活性Rap 1。Rap 1与afadin的结合对于afadin和酪氨酸磷酸酶SHP-2向前沿的募集是必要的。SHP-2被认为是紧密调节PDGF受体的激活及其下游信号通路的前沿形成。这些结果表明，afadin在PDGF诱导的定向细胞运动中具有新的作用，可能与活性Rap 1和SHP-2合作。
Afadin is an actin-filament-binding protein that binds to nectin, an immunoglobulin-like cell-cell adhesion molecule, and plays an important role in the formation of adherens junctions. Here, we show that afadin, which did not bind to nectin and was localized at the leading edge of moving cells, has another role: enhancement of the directional, but not random, cell movement. When NIH3T3 cells were stimulated with platelet-derived growth factor (PDGF), afadin colocalized with PDGF receptor, alpha v beta 3 integrin and nectin-like molecule-5 at the leading edge and facilitated the formation of leading-edge structures and directional cell movement in the direction of PDGF stimulation. However, these phenotypes were markedly perturbed by knockdown of afadin, and were dependent on the binding of afadin to active Rap1. Binding of Rap1 to afadin was necessary for the recruitment of afadin and the tyrosine phosphatase SHP-2 to the leading edge. SHP-2 was previously reported to tightly regulate the activation of PDGF receptor and its downstream signaling pathway for the formation of the leading edge. These results indicate that afadin has a novel role in PDGF-induced directional cell movement, presumably in cooperation with active Rap1 and SHP-2.