Membrane lipids, EGF receptors, and intracellular signals colocalize and are polarized in epithelial cells moving directionally in a physiological electric field
Membrane lipids, EGF receptors, and intracellular signals colocalize and are polarized in epithelial cells moving directionally in a physiological electric field
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DOI：
10.1096/fj.01-0811fje
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发表时间：
2002-04-01
期刊：
影响因子：
4.8
通讯作者：
McCaig, CD
中科院分区：
文献类型：
--
作者：
Zhao, M;Pu, J;McCaig, CD
定向细胞迁移对于组织形成、炎症和伤口愈合是必不可少的。趋化性在这些情况下起主要作用，并由不对称的细胞内信号支持。内源性电场(EFS)在细胞发生运动的地方是常见的，例如在伤口愈合过程中，细胞通过重新定向和定向迁移(趋电/趋电)来响应电场梯度。我们发现，生理性的EF不对称地重新分布EGF(表皮生长因子)受体和不溶于洗涤剂的膜脂，导致阴极极化和MAP激酶ERK1/2的激活。这诱导了定向迁移的哺乳动物上皮细胞的前沿肌动蛋白聚合。抑制EGF受体-MAP激酶信号通路显著减少前沿肌动蛋白的不对称性和定向迁移。我们提出了一个模型，在这个模型中，EF极化的膜脂域和EGF受体通过MAP激酶引起不对称信号，从而驱动细胞的定向迁移。与支持趋化作用的机制进行了比较。
Directed cell migration is essential for tissue formation, inflammation, and wound healing. Chemotaxis plays a major role in these situations and is underpinned by asymmetric intracellular signaling. Endogenous electric fields (EFs) are common where cell movement occurs, such as in wound healing, and cells respond to electric field gradients by reorienting and migrating directionally (galvanotaxis/electrotaxis). We show that a physiological EF redistributed both EGF (epidermal growth factor) receptors and detergent-insoluble membrane lipids asymmetrically, leading to cathodal polarization and enhanced activation of the MAP kinase, ERK1/2. This induced leading-edge actin polymerization in directionally migrating mammalian epithelial cells. Inhibiting the EGF receptor-MAP kinase signaling pathway significantly decreased leading edge actin asymmetry and directional migration. We propose a model in which EF-polarized membrane lipid domains and EGF receptors cause asymmetric signaling through MAP kinase, which drives directional cell migration. A comparison is made with the mechanisms underpinning chemotaxis.