Polarity and cell fate asymmetry in Caulobacter crescentus

Abstract

The production of asymmetric daughter cells is a hallmark of metazoan development and critical to the life cycle of many microbes, including the α-proteobacterium Caulobacter crescentus. For Caulobacter, every cell division is asymmetric, yielding daughter cells with different morphologies and replicative potentials. This asymmetry in daughter cell fate is governed by the response regulator CtrA, a transcription factor that can also bind and silence the origin of replication. CtrA activity is controlled by a complex regulatory circuit that includes several polarly localized histidine kinases. This circuit ensures differential activation of CtrA in daughter cells, leading to their asymmetric replicative potentials. Here, we review progress in elucidating the molecular mechanisms regulating CtrA and the role of cellular polarity in this process.

Figure 1

Asymmetric cell division in bacteria. (a) For all rod-shaped bacteria, cell division yields daughter cells with poles of different ages, one created by the most recent division and one created by an earlier division. (b) Schematic of the Caulobacter crescentus life cycle indicating the asymmetric division that produces daughter cells with different polar morphologies and replicative capacities. Morphological and cell cycle stages are indicated above and below, respectively, the diagram.

Figure 2

Regulation of CtrA and replicative asymmetry in Caulobacter. (a) Summary of the regulatory circuitry that controls CtrA in a cell type-specific manner, including the subcellular localization patterns of the histidine kinases CckA, DivL, PleC, and DivJ. (b) Model of the two-component signaling pathways and protein–protein interactions that regulate CtrA. CckA initiates a phosphorelay that culminates in phosphorylation and activation of CtrA. The activation of CckA as a kinase depends on DivL. Phosphorylated DivK can inhibit the CckA–DivL complex. DivK phosphorylation is controlled by a cognate kinase, DivJ, and phosphatase, PleC, which localize to opposite poles of the predivisional cell and to opposite daughter cells, thereby imposing cell type-specificity on CtrA activation. Reprinted, with permission, from [28^••].