Unique Signaling Logic within a Bacterial Cell Cycle Circuit

A fundamental hallmark of diverse organisms from stem cells to bacteria is asymmetric cell division orchestrated by subcellular protein localization. One of the simplest organisms to undergo an asymmetric cell division is the gram-negative bacterium Caulobacter crescentus. Critically, Caulobacter's asymmetric cell pole development is coordinated with cell division by a network of localized two-component systems (TCS). While many of the signaling players are known, the mechanistic wiring within this network is poorly understood.Here we examined the role of how the pseudokinase DivL couples together two signaling pathways through binding to the response regulator DivK. We identified point mutations that disrupt DivL-DivK binding, and evaluate the ability of these DivL mutants to localize to the cell poles. Unexpectedly, we observed DivL's sensor domain plays a role in specifically binding DivK∼P over unphosphorylated DivK. As well, we characterize the impact of the cell cycle histidine kinase CckA upon the DivL-DivK interaction. Taken together we propose a model for how the pseudo-kinase DivL has re-wired it's catalytic HK domain to detect the cytokinesis signal DivK∼P and directly modulate the activity of CckA enabling complex cell-fate decision making.