To ensure that each daughter cell receives a single genomic complement at the end of cell division, the central spindle—a set of microtubule bundles that forms between the separating chromosomes during anaphase—controls assembly and constriction of a cortical contractile actomyosin ring that bisects the separated chromosome masses. A key regulator of signaling by the central spindle is the protein complex centralspindlin. The current dominant model for signaling during cytokinesis proposes a simple positive signaling cascade in which centralspindlin tethers a Rho guanine nucleotide exchange factor (RhoGEF) to the central spindle, thereby activating the small GTPase RhoA locally at the cell equator. RhoA and its effectors, in turn, direct assembly and constriction of the contractile ring that divides the cell. Now Canman et al. challenge this view by demonstrating that the critical function of centralspindlin in promoting contractile ring constriction is the negative regulation of Rac, a different Rho family GTPase. Thus centralspindlin may inactivate Rac and its effectors at the cell equator, and it is this negative regulation that promotes the RhoA-dependent constriction of the contractile ring.
J. C. Canman, L. Lewellyn, K. Laband, S. J. Smerdon, A. Desai, B. Bowerman, K. Oegema, Inhibition of Rac by the GAP activity of centralspindlin is essential for cytokinesis. Science 322, 1543–1546 (2008). [Abstract] [Full Text]