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Chapter 17 : Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of

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Abstract:

Morphogenesis in appears to be driven by internal cues, with stages of the cell division cycle acting as checkpoints for specific developmental events. Genetic studies have identified signal transduction pathways mediated by members of the His-Asp phosphorelay proteins that are essential both for cell cycle control and developmental regulation. These pathways provide a molecular mechanism for the coordination of developmental events with cell cycle progression. The strains were classified as either or mutants, depending on whether DNA replication is blocked at the nonpermissive temperature. mutants blocked in either DNA chain initiation (DNAi) or DNA chain elongation (DNAe) fail to complete DNA synthesis (DNAc). In addition to their functions in adaptation to environmental changes, some of these signal transduction proteins also play essential roles in developmental and cell cycle regulation. In one model, activation of the signal transduction pathway controlling PleD during the swarmer-to-stalked-cell transition leads to flagellum ejection and loss of motility, and the PleC-DivK signal transduction pathway functions in late predivisional cells to initiate motility. Other signal transduction proteins that remain to be identified are those regulating activation of flagellar rotation in response to the PleC kinase and the protein kinase or kinases that presumably regulate the PleD-mediated loss of motility and stalk formation. A major goal of future research will be to identify the cell cycle, and possibly environmental, cues to which these and other signal transduction pathways respond.

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
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Figures

Image of FIGURE 1
FIGURE 1

cell cycle. Developmental events in the wild-type strain CB15 include flagellum formation (Fla), activation of flagellum rotation (Mot), appearance of polar bacteriophage receptors (ϕ), pilus formation (Pili), flagellum ejection and loss of motility (Mot), and stalk formation (Stk). The periods corresponding to presynthetic gap (G1), DNA synthesis (S), and postsynthetic gap (G2) are indicated.

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
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Image of FIGURE 2
FIGURE 2

Organization of DNA synthetic and cell division pathways. Cell cycle events on the DNA synthetic and cell division pathways are defined in the text. The functional dependency of the gene-mediated steps was determined by reciprocal shift experiments with TS mutations in or genes (shown in parentheses) in combination with the reversible inhibitor hydroxyurea (HU) or penicillin G (Pen) ( ). †, homologues of genes expected to act in initiation of DNA replication and DNA chain elongation (see the text and chapter 18). These genes were not examined in the epistasis experiments. G1, S, G2, see the legend to Fig. 1 .

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
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Image of FIGURE 3
FIGURE 3

Developmental phenotypes of cell division cycle and mutant cells. The diagrams depict the cellular morphology of mutations in cell cycle and developmental genes that affect polar morphogenesis. (A) mutant blocked in DNAe; mutant blocked in DIVp; (C) mutant blocked in CS; (D) mutant blocked in the swarmer-to-stalked-cell transition. The ability or failure of the mutants to execute flagellum biosynthesis (Fla), gain motility (Mot), and make stalks (Stk) is shown by + and -, respectively.

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
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Image of FIGURE 4
FIGURE 4

Predicted domain organization of HPKs and response regulators. The cross-hatched boxes in kinases PleC, DivJ, and DivL indicate predicted transmembrane regions. The conserved sequence motifs in the H, N, D, F, and G boxes of the catalytic domains are shown in Table 1 . The receiver domains of response regulators DivK, PleD, CtrA, and FlbD are shown by cross-hatched boxes. Residues corresponding to Asp-57 (D), the presumptive site of phosphorylation, and the conserved Asp-13 (D) and Lys-109 (K) in CheY are indicated for each of the proteins. The helix-turn-helix (HTH) motifs of CtrA and FlbD represent the predicted DNA binding domains. D and D′ (cross-hatched boxes) are the two putative receiver domains, and GGEEF is the carboxy-terminal conserved domain of PleD.

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
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Image of FIGURE 5
FIGURE 5

Model for the organization of signal transduction pathways regulating differentiation and cell division. This model indicates possible cell cycle cues or checkpoints that may regulate signal transduction and development (see the text). The DivL-CtrA and DivJ-DivK pathways presumably function during mid-S phase. CtrA accumulates at this time in early predivisional cells, when it is required for repression of premature initiation of DNA replication, activation of class II flagellar genes, and regulation of other cell cycle genes (reviewed in chapter 18). Dashed arrows indicate proposed signal transduction pathways.

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
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References

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Tables

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TABLE 1

Subfamilies of histidine protein kinases

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
Generic image for table
TABLE 2

Histidine protein kinases of five bacterial species

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17
Generic image for table
TABLE 3

Classification of response regulators based on receiver and output domains members

Citation: Ohta N, Grebe T, Newton A. 2000. Signal Transduction and Cell Cycle Checkpoints in Developmental Regulation of , p 341-359. In Brun Y, Shimkets L (ed), Prokaryotic Development. ASM Press, Washington, DC. doi: 10.1128/9781555818166.ch17

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