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  • Review Article
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Spatial control of bacterial division-site placement

Key Points

  • In most prokaryotes, and indeed eukaryotes, after chromosome replication and segregation of the daughter chromosomes to the two halves of the cell, cell division takes place and two progeny cells are formed. Division occurs by formation of a division septum, usually at midcell. The accurate placement of the division site is essential for the propagation of the species. In bacteria, most work on division-site selection has been carried out in Escherichia coli and Bacillus subtilis, both of which are rod-shaped species.

  • During normal cell division in E. coli, accurate placement of the division site is accomplished by the Min site-selection system, which comprises three Min proteins: a division inhibitor, MinC; a membrane-assembly protein, MinD; and a topological-specificity factor, MinE.

  • MinC inhibits cell division by preventing the formation of FtsZ rings, an essential first step in cell division. As MinC activity is not site-specific, MinE must prevent MinC from blocking division at midcell, the normal division site. In E. coli it does so by organizing the MinCDE proteins into a membrane-associated polar zone that extends from the cell pole towards midcell. The polar zone is prevented from extending past midcell owing to the formation of a MinE ring that acts as a 'stop-growth' signal. As MinC cannot reach midcell, cell division is prevented at the cell pole and polar zone, but not at midcell. To prevent cell division occurring at the opposite pole, the polar zone and E-ring then rapidly disassemble and reassemble at the opposite pole.

  • Therefore, the Min system controls accurate placement of the division site by ensuring the absence of MinC, the division inhibitor, at midcell. Evidence from B. subtilis suggests that the Min system also might specifically inactivate potential division sites at the cell poles, possibly owing to the residual presence at the poles of division components or factors carried over from the preceding division event.

  • MinC and MinD homologues are present in many Gram-positive and Gram-negative species. MinE (in Gram-negative bacteria) and its apparent functional homologue DivIVA (in Gram-positive bacteria) are also widely distributed. However, there are variations; for example, there is no pole-to-pole oscillation in B. subtilis, and some bacteria, such as Caulobacter crescentus, have no Min homologues.

  • Whereas the Min system has a dominant role in bacterial division-site placement under normal conditions, a second division site regulatory system, the nucleoid-occlusion system, ensures that the division septum is not formed over nucleoids, thereby preventing the transection of chromosomal material, which would be a lethal event. Nucleoid occlusion functions in cells in which nucleoid replication or segregation are impaired or when the Min system is absent. Two nucleoid-occlusion proteins have recently been identified — Noc in B. subtilis and SlmA in E. coli. Although these proteins show little sequence similarity, they are both division inhibitors that are associated with nucleoids and prevent the formation of division septa in the region of the nucleoid.

Abstract

The site of cell division in bacterial cells is placed with high fidelity at a designated position, usually the midpoint of the cell. In normal cell division in Escherichia coli this is accomplished by the action of the Min proteins, which maintain a high concentration of a septation inhibitor near the ends of the cell, and a low concentration at midcell. This leaves the midcell site as the only available location for formation of the division septum. In other species, such as Bacillus subtilis, this general paradigm is maintained, although some of the proteins differ and the mechanisms used to localize the proteins vary. A second mechanism of negative regulation, the nucleoid-occlusion system, prevents septa forming over nucleoids. This system functions in Gram-negative and Gram-positive bacteria, and is especially important in cells that lack the Min system or in cells in which nucleoid replication or segregation are defective. Here, we review the latest findings on these two systems.

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Figure 1: The MinCDE oscillation cycle.
Figure 2: The helical organization of the Min system.
Figure 3: The mechanism of polar-zone assembly and disassembly.
Figure 4: The nucleoid occlusion system.
Figure 5: The relationship of FtsZ rings and coils to the formation of the polar septum in sporulating cells.

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Acknowledgements

We acknowledge helpful discussions with Dr M. J. Osborn. Work from the authors' laboratory was supported by a grant from the U.S. National Institutes of Health.

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Correspondence to Lawrence Rothfield.

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DATABASES

Entrez

Arabidopsis thaliana

Bacillus subtilis

Caulobacter crescentus

Escherichia coli

Neisseria gonorrhoeae

Schizosaccharomyces pombe

Thermotoga maritima

Shigella flexneri

Entrez Gene

ftsZ

minC

minD

minE

mreB

Swiss-Prot

DivIVA

FtsZ

MinC

MinD

MinE

MreB

SlmA

Noc

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Rothfield, L., Taghbalout, A. & Shih, YL. Spatial control of bacterial division-site placement. Nat Rev Microbiol 3, 959–968 (2005). https://doi.org/10.1038/nrmicro1290

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