Controlling the switches: Rho GTPase regulation during animal cell mitosis - PubMed (original) (raw)

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Controlling the switches: Rho GTPase regulation during animal cell mitosis

Yan Zuo et al. Cell Signal. 2014 Dec.

Abstract

Animal cell division is a fundamental process that requires complex changes in cytoskeletal organization and function. Aberrant cell division often has disastrous consequences for the cell and can lead to cell senescence, neoplastic transformation or death. As important regulators of the actin cytoskeleton, Rho GTPases play major roles in regulating many aspects of mitosis and cytokinesis. These include centrosome duplication and separation, generation of cortical rigidity, microtubule-kinetochore stabilization, cleavage furrow formation, contractile ring formation and constriction, and abscission. The ability of Rho proteins to function as regulators of cell division depends on their ability to cycle between their active, GTP-bound and inactive, GDP-bound states. However, Rho proteins are inherently inefficient at fulfilling this cycle and require the actions of regulatory proteins that enhance GTP binding (RhoGEFs), stimulate GTPase activity (RhoGAPs), and sequester inactive Rho proteins in the cytosol (RhoGDIs). The roles of these regulatory proteins in controlling cell division are an area of active investigation. In this review we will delineate the current state of knowledge of how specific RhoGEFs, RhoGAPs and RhoGDIs control mitosis and cytokinesis, and highlight the mechanisms by which their functions are controlled.

Keywords: Cytokinesis; Mitosis; Rho GTPase; RhoGAP; RhoGEF.

Copyright © 2014 Elsevier Inc. All rights reserved.

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Figures

Fig. 1

Fig. 1

Roles of Rho GTPases in mitosis and cytokinesis. A) Centrosome separation. Centrosome separation and convergence forces are denoted with arrows. Occurs in G2 and prophase. B) Mitotic spindle-kinetochore attachment stability and generation of cortical rigidity. Cortical F-actin is shown in red. Kinetochores are shown as green circles within condensed DNA. Occurs in prophase through metaphase. C) Cleavage furrow formation; contraction ring formation and constriction. Occurs during anaphase, telophase and cytokinesis.

Fig. 2

Fig. 2

RhoGEFs in mitosis and cytokinesis.

Fig. 3

Fig. 3

RhoGAPs in mitosis and cytokinesis.

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