Role of the microtubule cytoskeleton in modulating Cdc42 GTPase dynamics in the control of cell polarity.
The conserved GTPase Cdc42 is a key regulator of cell polarity and morphogenesis that controls processes such as actin-cable polymerization and exocyst localization. In fission yeast, Cdc42 activation exhibits oscillatory dynamics at the two polar growth zones. Anticorrelated oscillations at the cell tips result from positive and delayed negative feedbacks and competition for Cdc42 activators. One of these activators, the guanine nucleotide exchange factor (GEF) Gef1, undergoes a phosphorylation–dephosphorylation cycle that regulates its localization to its site of action at the cell cortex. Cortical localization of Gef1 is hypothesized to be dependent on microtubule-based delivery of a phosphatase to the cell tips. This project will model the potential role of the microtubule cytoskeleton in modulating levels of Gef1 and oscillations of Cdc42 at the cell cortex.