Spatiotemporal Regulation of RhoA during Cytokinesis

• Published in: Current biology Vol. 28; no. 9; pp. R570 - R580
• Main Authors: Basant, Angika, Glotzer, Michael
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 07-05-2018
• Subjects: Animals; Cell Membrane - metabolism; Cytokinesis - physiology; Embryonic Development - physiology; GTP Phosphohydrolases - metabolism; Humans; Microtubule-Associated Proteins - metabolism; Rho Guanine Nucleotide Exchange Factors - metabolism; rhoA GTP-Binding Protein - metabolism; rhoA GTP-Binding Protein - physiology; Spatio-Temporal Analysis; Spindle Apparatus - metabolism
• ISSN: 0960-9822; 1879-0445
• DOI: 10.1016/j.cub.2018.03.045

The active form of the small GTPase RhoA is necessary and sufficient for formation of a cytokinetic furrow in animal cells. Despite the conceptual simplicity of the process, the molecular mechanisms that control it are intricate and involve redundancy at multiple levels. Here, we discuss our current knowledge of the mechanisms underlying spatiotemporal regulation of RhoA during cytokinesis by upstream activators. The direct upstream activator, the RhoGEF Ect2, requires activation due to autoinhibition. Ect2 is primarily activated by the centralspindlin complex, which contains numerous domains that regulate its subcellular localization, oligomeric state, and Ect2 activation. We review the functions of these domains and how centralspindlin is regulated to ensure correctly timed, equatorial RhoA activation. Highlighting recent evidence, we propose that although centralspindlin does not always prominently accumulate on the plasma membrane, it is the site where it promotes RhoA activation during cytokinesis.
Basant and Glotzer review how RhoA activity is regulated to ensure correct timing and placement of cytokinesis.