Spatial complexity and control of a bacterial cell cycle

Abstract

A major breakthrough in understanding the bacterial cell cycle is the discovery that bacteria exhibit a high degree of intracellular organization. Chromosomal loci and many protein complexes are positioned at particular subcellular sites. In this review, we examine recently discovered control mechanisms that make use of dynamically localized protein complexes to orchestrate the Caulobacter crescentus cell cycle. Protein localization, notably of signal transduction proteins, chromosome partition proteins, and proteases, serves to coordinate cell division with chromosome replication and cell differentiation. The developmental fate of daughter cells is decided before completion of cytokinesis, via the early establishment of cell polarity by the distribution of activated signaling proteins, bacterial cytoskeleton, and landmark proteins.

Figure 1. The Caulobacter cell cycle and its regulation by master regulators

(A) Schematic of the Caulobacter cell cycle. Cell cycle events are shown in boxes that are aligned with the cell cycle model to show when these events take place during the cell cycle. (B) Schematic of the differential accumulation of the three master regulators during the Caulobacter cell cycle. Red indicates CtrA, green indicates DnaA, and blue indicates GcrA. The approximate number of genes included in the regulon of each master regulator is also indicated.

Figure 2. Spatial regulation of CtrA proteolysis

(A) A diagram of the regulatory pathways controlling the synthesis, the stability, and the activation of master transcriptional regulators. Protein names highlighted in pink correspond to proteins that localize at specific sub-cellular positions. (B) Model of the cell cycle-dependent localization of proteins involved in the degradation of the CtrA global regulator [14,15,16].

Figure 3. Regulation and localization of proteins involved in the polarization of Caulobacter cells

(A) A schematic diagram of the sequential proteolytic processing of PodJ, first by the periplasmic protease PerP, then by the Rip metalloprotease MmpA, and finally by an unknown cytoplasmic protease [21]. (B) A schematic of the regulatory pathway controlling the polarity determinant PodJ. SW pole indicates the flagellated pole of the pre-divisional cell. PodJL is synthesized in early pre-divisional cells, where it localizes at the SW pole and recruits PleC. Compartmentalization, monitored in part by PleC, activates the expression of the PerP protease. PerP cleaves PodJL into PodJS. The polar functions controlled by PodJL and PodJS are indicated [–24]. (C) Model of the cell cycle-dependent localization of proteins involved in polar in PodJ processing and polar organelles development. (D) Model of the cell cycle-dependent localization of the polarity determinant TipN. The new pole of the cell is marked by TipN throughout the cell cycle [29,30].

Figure 4. Integration of the spatial deployment of the replication origin and the mid-cell placement of FtsZ cytokinetic ring in Caulobacter

In swarmer cells (SW), the single origin of replication (Cori) is located at the flagellated cell pole and the FtsZ tubulin is at the opposite pole. After the initiation of replication, one copy of the Cori moves to the opposite end of the cell. The ParB partition protein in complex with the MipZ ATPase binds to the origin regions that are then localized at the two cell poles in the stalked cells. MipZ, an inhibitor of FtsZ polymerization, is distributed in a bipolar gradient with the highest concentrations at the poles and lowest at mid-cell. As soon as MipZ reaches the cell pole, FtsZ is displaced from that pole and moves to mid-cell, thereby marking the site of the cell division plane [34]. SW, swarmer cell; ST, stalked cell; PD, pre-divisional cell.