(2014-02-25) Atkins, Benjamin David; Pellman, David Steven; Winston, Fred; Reck-Peterson, Samara; McCollum, Dannel; Burgess, David
Rho GTPases are highly conserved regulators of cell polarity and the actin cytoskeleton. The role of the Rho GTPase Cdc42 and its regulation during cell division is not well understood. Using biochemical and imaging approaches in budding yeast, I demonstrate that Cdc42 activation peaks during the G1/S transition and during anaphase, but drops during mitotic exit and cytokinesis. Cdc5/Polo kinase is an important upstream cell cycle regulator that suppresses Cdc42 activity. Failure to downregulate Cdc42 during mitotic exit prevents the normal localization of key cytokinesis regulators - Iqg1 and Inn1- at the division site, and results in an abnormal septum. The effects of Cdc42 hyperactivation are largely mediated by the Cdc42 effector p21-activated kinase (PAK) kinase, Ste20. Inhibition of Cdc42 and related Rho GTPases may be a general feature of cytokinesis in eukaryotes.
