Department of Biology, Concordia University, Montreal, QC, Canada.
Small GTPases. 2022 Jan;13(1):211-224. doi: 10.1080/21541248.2021.1957384. Epub 2021 Aug 18.
Cytokinesis is required to cleave the daughter cells at the end of mitosis and relies on the spatiotemporal control of RhoA GTPase. Cytokinesis failure can lead to changes in cell fate or aneuploidy, which can be detrimental during development and/or can lead to cancer. However, our knowledge of the pathways that regulate RhoA during cytokinesis is limited, and the role of other Rho family GTPases is not clear. This is largely because the study of Rho GTPases presents unique challenges using traditional cell biological and biochemical methods, and they have pleiotropic functions making genetic studies difficult to interpret. The recent generation of optogenetic tools and biosensors that control and detect active Rho has overcome some of these challenges and is helping to elucidate the role of RhoA in cytokinesis. However, improvements are needed to reveal the role of other Rho GTPases in cytokinesis, and to identify the molecular mechanisms that control Rho activity. This review examines some of the outstanding questions in cytokinesis, and explores tools for the imaging and control of Rho GTPases.
有丝分裂末期的胞质分裂需要将子细胞切开，这依赖于 RhoA GTP 酶的时空控制。胞质分裂失败可导致细胞命运改变或非整倍体，这在发育过程中可能有害，或导致癌症。然而，我们对胞质分裂过程中调节 RhoA 的途径的了解有限，其他 Rho 家族 GTP 酶的作用也不清楚。这在很大程度上是因为使用传统的细胞生物学和生化方法研究 Rho GTP 酶存在独特的挑战，并且它们具有多功能性，使得遗传研究难以解释。最近一代的光遗传学工具和生物传感器可以控制和检测活性 Rho，这克服了其中的一些挑战，并有助于阐明 RhoA 在胞质分裂中的作用。然而，需要改进这些工具来揭示其他 Rho GTP 酶在胞质分裂中的作用，并确定控制 Rho 活性的分子机制。本文综述了胞质分裂中的一些悬而未决的问题，并探讨了 Rho GTP 酶的成像和控制工具。
