Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3
Numb controls integrin endocytosis for directional cell migration with aPKC and PAR-3
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DOI：
10.1016/j.devcel.2007.05.003
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发表时间：
2007-07-01
影响因子：
11.8
通讯作者：
Kaibuchi, Kozo
中科院分区：
文献类型：
--
作者：
Nishimura, Takashi;Kaibuchi, Kozo
迁移的细胞扩展了突起，以在其领先边缘建立新的粘附位点。细胞迁移的驱动力之一是细胞粘附分子（例如整联蛋白）的定向运输。在这里，我们表明内吞衔接子蛋白麻木是迁移细胞中定向整合蛋白运输的机械的重要组成部分。 Numb与整联蛋白βS结合，并定位于前缘底部底部底部的网状蛋白包被结构（CC; SS）。 RNAi的麻木抑制作用会损害整联蛋白内吞作用和细胞向整合素底物的迁移。 Numb受磷酸化的调节，因为该蛋白质是从CCSS释放出来的，并且当通过非典型蛋白激酶C（APKC）磷酸化时不再结合整联蛋白。由于Numb与APKC结合伴侣PAR-3相互作用，因此我们提出了一个模型，在该模型中，极化麻木磷酸化通过将整合素内吞作用引导到前缘有助于细胞迁移。
Migrating cells extend protrusions to establish new adhesion sites at their leading edges. One of the driving forces for cell migration is the directional trafficking of cell-adhesion molecules such as integrins. Here, we show that the endocytic adaptor protein Numb is an important component of the machinery for directional integrin trafficking in migrating cells. Numb binds to integrin-beta s and localizes to clathrin-coated structures (CC;Ss) at the substratum-facing surface of the leading edge. Numb inhibition by RNAi impairs both integrin endocytosis and cell migration toward integrin substrates. Numb is regulated by phosphorylation since the protein is released from CCSs and no longer binds integrins when phosphorylated by atypical protein kinase C (aPKC). Because Numb interacts with the aPKC binding partner PAR-3, we propose a model in which polarized Numb phosphorylation contributes to cell migration by directing integrin endocytosis to the leading edge.