Figure 1.
Physiology of the cell division cycle in Caulobacter crescentus.
Three cell cycle phases can be distinguished (from the left to the right): a DNA synthesis (S) phase that takes approximately 90 min, a cell division (G2/M) phase, lasting approximately 30 min, that culminates in the separation of mother (stalked) and daughter (swarmer) cells, and a growth and differentiation (G1-like) phase of the swarmer cell that lasts approximately 30 min. The color scheme denotes protein variations through the cell division cycle: GcrA (blue), CtrA (red), DnaA (green). The θ-like structure denotes replicating DNA. The ring in the middle of the cell indicates Z-ring assembly and constriction, leading to cell separation (cytokinesis). Symbols of different shapes at the two cell poles denote localization of proteins. Their identities are listed at the right of this figure. PD, predivisional. At the bottom, the time scale and important cell cycle-related physiological events are indicated.
Figure 2.
All proteins (ovals) are assumed to be produced and degraded at specific rates. Only degradation of CtrA and CtrA∼P is depicted explicitly (4 small circles indicate products of degradation), in order to show how these steps are regulated. Solid lines correspond to the mass flow while dashed lines denote regulatory effects. P1 and P2 denote the two promoters controlling CtrA production. Purple lines signify the role of localization/delocalization effects in corresponding regulations. The double-stranded closed curve at the bottom left represents DNA. Cori is the origin of DNA replication and Ter stands for the termination site. DNA methylation sites on genes are marked by cyan stars. Z-ring closure at the far right blocks the flux of DivK and DivK∼P between swarmer and stalked cell compartments.
Figure 3.
Correlations between protein levels and the physiological features of a dividing Caulobacter cell.
Time courses of protein expressions, DNA replication and Z-ring states produced by our model for the swarmer cell cycle (A, B) and for the stalked cell cycle (D, E). Physiological changes during cell cycle progression are shown in panel C.
Figure 4.
Simulated variations of proteins and other model state variables during the swarmer wild-type cell cycle.
Simulation begins with initiation of DNA replication. Three cell cycles are shown. Experimental data presented on some panels by open circles and squares, crosses and asterisks are re-plotted from the following sources: (A) Total DNA from Figure 4 in [84]. (B) CcrM from Figure 2 in [85]. (C) FtsZ from Fig. 2C in [86]; Zring from Fig. 3C in [87]; FtsQ from figure 2 in [86]. (D) Z from Figure 2 in [88]. (E) CtrA from Fig. 3C in [40]; CtrA∼P from Fig. 3C in [36]; GcrA from Figure 3 in [40]; DnaA from Figure 5 in [89]. (F) PodJL/PleC from Fig. 1A in [55] and Fig. 1B in [34]; DivJ from Fig. 2B in [33]; PerP from Fig. 4 in [55]. (G) DivK∼P from Figure 2 in [85]. (H) CckA∼P from Fig. 3B in [36]; CpdR from Fig. 5A in [35]; RcdA from Fig. 2C in [38].
Figure 5.
Simulation of ctrAD51E mutant.
ks,ctrA-P1 = ks,ctrA-P2 = 0, ktrans,CtrA∼P = 0, k ′ = 0.064 (40% of WT) was added to [CtrA∼P] equation. The vertical column of open circles here and on subsequent figures indicates the time at which the mutation is introduced. For earlier times the simulation is run with wild-type values of all parameters.
Figure 6.
kd,ctrA2 = 0.0375 (15% of WT).
Figure 7.
Simulation of double mutant ctrAD51EΔ3Ω.
ks,ctrA-P1 = ks,ctrA-P2 = 0, ktrans,CtrA∼P = 0, k ′ = 0.064 (40% of WT) was added to [CtrA∼P] equation, kd,ctrA2 = 0.0375 (15% of WT).
Figure 8.
Simulation of ctrA constitutive expression.
ctrA is constitutively expressed at 30% of its wild-type promoter activity: ks,ctrA-P1 = ks,ctrA-P2 = 0, k ′ = 0.048.
Figure 9.
k ′ = 0.16.
Figure 10.
ks,DivJ1 = ks,DivJ2 = 0.
Figure 11.
Simulation of ΔpleC/ΔpodJ mutants.
ks,PodJL = 0.
Figure 12.
Simulation of pleCop/podJop mutant.
ks,PodJL = 0, k′ = 0.043 (100% of WT).
Figure 13.
Simulation of unphosphorylated CckA mutant.
ktrans,CckA = 0.