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首页> 外文期刊>Molecular biology of the cell >Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration
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Subcellular optogenetic activation of Cdc42 controls local and distal signaling to drive immune cell migration

机译：Cdc42的亚细胞光遗传学激活控制局部和远侧信号，以驱动免疫细胞迁移

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摘要

Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the consequences of localized Cdc42 activation within an immune cell. Here we used subcellular optogenetics to determine how Cdc42 activation at one side of a cell affects both cell behavior and dynamic molecular responses throughout the cell. We found that localized Cdc42 activation is sufficient to generate polarized signaling and directional cell migration. The optically activated region becomes the leading edge of the cell, with Cdc42 activating Rac and generating membrane protrusions driven by the actin cytoskeleton. Cdc42 also exerts long-range effects that cause myosin accumulation at the opposite side of the cell and actomyosin-mediated retraction of the cell rear. This process requires the RhoA-activated kinase ROCK, suggesting that Cdc42 activation at one side of a cell triggers increased RhoA signaling at the opposite side. Our results demonstrate how dynamic, subcellular perturbation of an individual signaling protein can help to determine its role in controlling polarized cellular responses.
机译：迁移性免疫细胞使用细胞内信号网络生成并定向对细胞外信号的空间极化反应。单体G蛋白Cdc42被认为在控制极化反应中起重要作用，但是很难直接确定免疫细胞内Cdc42活化的后果。在这里，我们使用亚细胞光遗传学来确定细胞一侧的Cdc42激活如何影响整个细胞的细胞行为和动态分子反应。我们发现，本地化的Cdc42激活足以产生极化信号和定向细胞迁移。光学激活区域成为细胞的前缘，而Cdc42激活Rac并产生由肌动蛋白细胞骨架驱动的膜突起。 Cdc42还发挥了远距离作用，导致肌球蛋白在细胞的另一侧积聚，并由肌动球蛋白介导的细胞后部缩回。此过程需要RhoA激活的激酶ROCK，这表明细胞一侧的Cdc42激活会触发另一侧的RhoA信号传导增加。我们的结果表明，单个信号蛋白的动态亚细胞扰动如何帮助确定其在控制极化细胞反应中的作用。

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