Synergistic regulation of the Cdc42 GTPase cycle

Emergent properties of a system arise when the systems parts interact in a wider whole. An example of such an emergent system is the cell division protein network of Saccharomyces cerevisiae. Here the cell division control protein Cdc42 accumulates in a single spot at the cell membrane. Cdc42 is a membrane-binding Rho-type GTPase and a highly regulated protein, it’s interacting with GEFs, GAPs, scaffold and other regulatory proteins.

To shine more light on the emergent properties of the system, we investigated a process at the centre of Cdc42: its GTPase cycle. We studied the entire GTPase cycle of Cdc42 in vitro and the effect of non-specific protein-protein interactions, the GEF Cdc24, GAP Rga2, scaffold protein Bem1, and combinations thereof, on it.

We developed a mathematical model to describe the GTPase cycle and characterise Cdc42's properties. The GEF Cdc24 exhibits cooperativity, and our data suggests that it synergises with Rga2. Surprisingly, we also found that non-specific protein-protein interactions positively affect the Cdc42 GTPase cycle. Taken together, our data suggests that Cdc42's GTPase activity is a dynamic property that is contingent on both specific and non-specific interactions with other polarity proteins, and the synergies arising from those interaction.