Stanley Alanna, Thompson Kerry, Hynes Ailish, Brakebusch Cord, Quondamatteo Fabio
1 Skin and Extracellular Matrix Research Group , Anatomy, NUI Galway, Galway, Ireland .
Antioxid Redox Signal. 2014 May 1;20(13):2026-42. doi: 10.1089/ars.2013.5713. Epub 2014 Feb 21.
Rho GTPases are historically known to be central regulators of actin cytoskeleton reorganization. This affects many processes including cell migration. In addition, members of the Rac subfamily are known to be involved in reactive oxygen species (ROS) production through the regulation of NADPH oxidase (Nox) activity. This review focuses on relationships between Nox-regulated ROS, Rho GTPases, and cytoskeletal reorganization, in the context of cell migration.
It has become clear that ROS participate in the regulation of certain Rho GTPase family members, thus mediating cytoskeletal reorganization.
The role of the actin cytoskeleton in providing a scaffold for components of the Nox complex needs to be examined in the light of these new advances. During cell migration, Rho GTPases, ROS, and cytoskeletal organization appear to function as a complex regulatory network. However, more work is needed to fully elucidate the interactions between these factors and their potential in vivo importance.
Ultrastructural analysis, that is, electron microscopy, particularly immunogold labeling, will enable direct visualization of subcellular compartments. This in conjunction with the analysis of tissues lacking specific Rho GTPases, and Nox components will facilitate a detailed examination of the interactions of these structures with the actin cytoskeleton. In combination with the analysis of ROS production, including its subcellular location, these data will contribute significantly to our understanding of this intricate network under physiological conditions. Based on this, in vivo and in vitro studies can then be combined to elucidate the signaling pathways involved and their targets.
Rho GTP酶一直以来被认为是肌动蛋白细胞骨架重组的核心调节因子。这会影响包括细胞迁移在内的许多过程。此外，已知Rac亚家族成员通过调节NADPH氧化酶（Nox）活性参与活性氧（ROS）的产生。本综述聚焦于在细胞迁移背景下，Nox调节的ROS、Rho GTP酶和细胞骨架重组之间的关系。
现已明确ROS参与某些Rho GTP酶家族成员的调节，从而介导细胞骨架重组。
鉴于这些新进展，需要研究肌动蛋白细胞骨架为Nox复合体各组分提供支架的作用。在细胞迁移过程中，Rho GTP酶、ROS和细胞骨架组织似乎构成一个复杂的调节网络。然而，要全面阐明这些因素之间的相互作用及其在体内的潜在重要性，还需要开展更多工作。
超微结构分析，即电子显微镜检查，尤其是免疫金标记，将能够直接观察亚细胞区室。这与对缺乏特定Rho GTP酶和Nox组分的组织进行分析相结合，将有助于详细研究这些结构与肌动蛋白细胞骨架的相互作用。结合对ROS产生的分析，包括其亚细胞定位，这些数据将极大地有助于我们在生理条件下理解这个复杂的网络。基于此，随后可将体内和体外研究结合起来，以阐明所涉及的信号通路及其靶点。
