Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe 657-8501, Japan.
Cells. 2019 Jan 28;8(2):92. doi: 10.3390/cells8020092.
The small GTPases of the Rho-family (Rho-family GTPases) have various physiological functions, including cytoskeletal regulation, cell polarity establishment, cell proliferation and motility, transcription, reactive oxygen species (ROS) production, and tumorigenesis. A relatively large number of downstream targets of Rho-family GTPases have been reported for in vitro studies. However, only a small number of signal pathways have been established at the in vivo level. Cumulative evidence for the functions of Rho-family GTPases has been reported for in vivo studies using genetically engineered mouse models. It was based on different cell- and tissue-specific conditional genes targeting mice. In this review, we introduce recent advances in in vivo studies, including human patient trials on Rho-family GTPases, focusing on highly polarized sensory organs, such as the cochlea, which is the primary hearing organ, host defenses involving reactive oxygen species (ROS) production, and tumorigenesis (especially associated with RAC, novel RAC1-GSPT1 signaling, RHOA, and RHOBTB2).
Rho 家族的小分子 GTPases(Rho 家族 GTPases)具有多种生理功能,包括细胞骨架调节、细胞极性建立、细胞增殖和运动、转录、活性氧(ROS)产生和肿瘤发生。已经报道了大量 Rho 家族 GTPases 的体外研究的下游靶标。然而,仅在体内水平建立了少数信号通路。使用基因工程小鼠模型进行的体内研究报告了 Rho 家族 GTPases 的功能的累积证据。它基于针对小鼠的不同细胞和组织特异性条件基因。在这篇综述中,我们介绍了体内研究的最新进展,包括人类患者对 Rho 家族 GTPases 的试验,重点介绍了高度极化的感觉器官,如作为主要听觉器官的耳蜗、涉及活性氧(ROS)产生的宿主防御以及肿瘤发生(特别是与 RAC、新型 RAC1-GSPT1 信号、RHOA 和 RHOBTB2 相关)。