Bacteria that differentiate into morphologically and physiologically different daughter cells must coordinate cell cycle regulation with regulation of components specific to each of the distinct daughters. The bacterium Caulobacter crescentus divides asymmetrically into a motile swarmer cell and a stalked cell. One of the regulators of C. crescentus differentiation is the protein SpmX, which localizes to one pole of the dividing cell and recruits kinase DivJ, which is involved in specifying the stalked daughter cell through phosphorylation of DivK. Janakiraman et al. found that SpmX also influences global cell cycle regulation. Cells with a mutation in spmX had impaired DivJ phosphorylation of DivK accumulated in G2 phase. Strains with this spmX mutation that had also been randomly mutated had an increased frequency of disruptions in the gene encoding TacA and genes necessary for TacA expression, indicating that loss of TacA suppressed the spmX mutant phenotype. TacA oscillates in phase with cell cycle regulator CtrA, and phosphorylated TacA activates stalk biogenesis by promoting gene expression, including that of spmX. Bacteria with the spmX mutation had increased amounts of phosphorylated TacA, suggesting that SpmX is a negative regulator of TacA phosphorylation. A screen for genes with TacA-dependent expression identified a previously unknown protein, which the authors refer to as SpmY, which when deleted caused cellular elongation and arrest in G2. Fluorescently labeled SpmY localized to the stalked pole of dividing wild-type cells but not in cells with deletions of spmX or of divJ. Sequences homologous to spmY were present in published bacterial genomes, and overexpression of spmY from Brevundimonas subvibroides, another stalked bacterium, in mutant C. crescentus rescued the effect of the spmY mutation. Thus, bacterial proteins that regulate morphological differentiation also coordinate this process with cell cycle progression.
B. Janakiraman, J. Mignolet, S. Narayanan, P. H. Viollier, S. K. Radhakrishnan, In-phase oscillation of global regulons is orchestrated by a pole-specific organizer. Proc. Natl. Acad. Sci. U.S.A. 113, 12550–12555 (2016). [PubMed]