Rho GTPases in animal cell cytokinesis: An occupation by the one percent

Abstract

Rho GTPases are molecular switches that elicit distinct effects on the actomyosin cytoskeleton to accurately promote cytokinesis. Although they represent less than 1% of the human genome, Rho GTPases exert disproportionate control over cell division. Crucial to this master regulatory role is their localized occupation of specific domains of the cell to ensure the assembly of a contractile ring at the proper time and place. RhoA occupies the division plane and is the central positive Rho family regulator of cytokinesis. Rac1 is a negative regulator of cytokinesis and is inactivated within the division plane while active Rac1 occupies the cell poles. Cdc42 regulation during cytokinesis is less studied, but thus far a clear role has only been shown during polar body emission. Here we review what is known about the function of Rho family GTPases during cell division, as well as their upstream regulators and known downstream cytokinetic effectors.

Cytokinesis in Animal Cells

“…The contraction of these actomyosin filaments is currently seen as the major, although not the sole, driving force that triggers furrow ingression (Wang 2005). The small GTPase RhoA controls assembly and constriction of the contractile ring by activating two parallel signaling pathways Jordan and Canman 2012). On binding the diaphanous (Dia) members of formin-homology proteins, RhoA stimulates profilin-mediated actin polymerization (Fig.…”

Macrophage differentiation induced by PMA is mediated by activation of RhoA/ROCK signaling

“…It has been reported that RhoA/ ROCK signaling pathway regulated actin cytoskeleton and promoted actin myosin contraction, and subsequently regulated cell translocation and shrinkage (Ishizaki et al, 1996;Leung et al, 1996;Nobes and Hall, 1995;Ridley and Hall, 1992). In addition, the regulation of RhoA/ROCK signaling on actin cytoskeleton could also promote smooth muscle contraction, stress fiber formation, cell adhesion and differentiation (Chu et al, 2012;Jordan and Canman, 2012;Kishi et al, 2005;Lee et al, 2012;Maddox et al, 2012;Ruiz-Loredo et al, 2011).…”

The Aurora B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression

“…Once MgcRacGAP is phosphorylated by PLK1, ECT2 is recruited to the central spindle to activate RhoA (Burkard et al, 2009;Wolfe et al, 2009). Although this model clearly shows that MgcRacGAP is essential for RhoA activation, the functional role of the GAP domain remains elusive (Canman et al, 2008;Jordan and Canman, 2012;Loria et al, 2012). A recent study showed that MgcRacGAP inactivates Rac1 to promote furrowing in mammalian cells (Bastos et al, 2012); however, it remains unknown whether there are any mechanisms that regulate the GAP activity during cytokinesis.…”