Min System

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Displacement of the Z-ring and the Ter macrodomain in a long ΔslmA Δmin double mutant E. coli cell. Z-ring fluorescence is followed using a ZipA-GFP construct (green), while the chromosomal terminus is labeled with MatP-mCherry (red). A phase contrast image (gray) is overlaid to visualize the cell contour. The scale bar is 2 μm.

The Min System is a mechanism composed of three proteins MinC, MinD, and MinE used by E. coli as a means of properly localizing the septum prior to cell division. Each component participates in generating a dynamic oscillation of FtsZ protein inhibition between the two bacterial poles to precisely specify the mid-zone of the cell, allowing the cell to accurately divide in two. This system is known to function in conjunction with a second negative regulatory system, the nucleoid occlusion system (NO), to ensure proper spatial and temporal regulation of chromosomal segregation and division.

Contents

History

The initial discovery of this family of proteins is attributed to Adler et al. (1967). First identified as E. coli mutants that could not produce a properly localized septum, resulting in the generation of minicells [1] [2] due to mislocalized cell division occurring near the bacterial poles. This caused miniature vesicles to pinch off, void of essential molecular constituents permitting it to exist as a viable bacterial cell. Minicells are achromosomal cells that are products of aberrant cell division, and contain RNA and protein, but little or no chromosomal DNA. This finding led to the identification of three interacting proteins involved in a dynamic system of localizing the mid-zone of the cell for properly controlled cell division.[ citation needed ]

Function

The Min proteins prevent the FtsZ ring from being placed anywhere but near the mid cell and are hypothesized to be involved in a spatial regulatory mechanism that links size increases prior to cell division to FtsZ polymerization in the middle of the cell.[ citation needed ]

The MinCDE system. MinD-ATP binds to a cell pole, also binds MinC, which prevents the formation of FtsZ polymers. The MinE ring causes hydrolysis of MinD's bound ATP, turning it into ADP and releasing the complex from the membrane. The system oscillates as each pole builds up a concentration of inhibitor that is periodically dismantled. MinCDE System2.svg
The MinCDE system. MinD-ATP binds to a cell pole, also binds MinC, which prevents the formation of FtsZ polymers. The MinE ring causes hydrolysis of MinD's bound ATP, turning it into ADP and releasing the complex from the membrane. The system oscillates as each pole builds up a concentration of inhibitor that is periodically dismantled.

Centering the Z-Ring

One model of Z-ring formation permits its formation only after a certain spatial signal that tells the cell that it is big enough to divide. [3] The MinCDE system prevents FtsZ polymerization near certain parts of the plasma membrane. MinD localizes to the membrane only at cell poles and contains an ATPase and an ATP-binding domain. MinD is only able to bind to the membrane when in its ATP-bound conformation. Once anchored, the protein polymerizes, resulting in clusters of MinD. These clusters bind and then activate another protein called MinC, which has activity only when bound by MinD. [4] MinC serves as a FtsZ inhibitor that prevents FtsZ polymerization. The high concentration of a FtsZ polymerization inhibitor at the poles prevents FtsZ from initiating division at anywhere but the mid-cell. [5]

MinE is involved in preventing the formation of MinCD complexes in the middle of the cell. MinE forms a ring near each cell pole. This ring is not like the Z-ring. Instead, it catalyzes the release of MinD from the membrane by activating MinD's ATPase. This hydrolyzes the MinD's bound ATP, preventing it from anchoring itself to the membrane.

MinE prevents the MinD/C complex from forming in the center but allows it to stay at the poles. Once the MinD/C complex is released, MinC becomes inactivated. This prevents MinC from deactivating FtsZ. As a consequence, this activity imparts regional specificity to Min localization. [6] Thus, FtsZ can form only in the center, where the concentration of the inhibitor MinC is minimal. Mutations that prevent the formation of MinE rings result in the MinCD zone extending well beyond the polar zones, preventing FtsZ to polymerize and to perform cell division. [7] MinD requires a nucleotide exchange step to re-bind to ATP so that it can re-associate with the membrane after MinE release. The time lapse results in a periodicity of Min association that may yield clues to a temporal signal linked to a spatial signal. In vivo observations show that the oscillation of Min proteins between cell poles occurs approximately every 50 seconds. [8] Oscillation of Min proteins, however, is not necessary for all bacterial cell division systems. Bacillus subtilis has been shown to have static concentrations of MinC and MinD at the cell poles. [9] This system still links cell size to the ability to form a septum via FtsZ and divide.

in vitro Reconstitution

MinD (cyan) chased by MinE (magenta) to form spiraling waves on an artificial membrane Min Spirals.gif
MinD (cyan) chased by MinE (magenta) to form spiraling waves on an artificial membrane

The dynamic behavior of Min proteins has been reconstituted in vitro using artificial lipid bilayers, [10] with varying lipid composition [11] and different confinement geometry [12] as mimics for the cell membrane. The first pattern to be reconstituted were spiraling waves of MinD chased by MinE, [13] followed by the reconstitution of waves of all three proteins, MinD, MinE and MinC. [14] Importantly, MinD and MinE can self-organize into a wide variety of patterns depending on the reaction conditions. [15] [16]

Additional study is required to elucidate the extent of temporal and spatial signaling permissible by this biological function. These in vitro systems offered unprecedented access to features such as residence times and molecular motility.

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<span class="mw-page-title-main">FtsZ</span> Protein encoded by the ftsZ gene

FtsZ is a protein encoded by the ftsZ gene that assembles into a ring at the future site of bacterial cell division. FtsZ is a prokaryotic homologue of the eukaryotic protein tubulin. The initials FtsZ mean "Filamenting temperature-sensitive mutant Z." The hypothesis was that cell division mutants of E. coli would grow as filaments due to the inability of the daughter cells to separate from one another. FtsZ is found in almost all bacteria, many archaea, all chloroplasts and some mitochondria, where it is essential for cell division. FtsZ assembles the cytoskeletal scaffold of the Z ring that, along with additional proteins, constricts to divide the cell in two.

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The MinD protein is one of three proteins encoded by the minB operon and also a part of the ParA family of ATPases. It is required to generate pole to pole oscillations prior to bacterial cell division as a means of specifying the midzone of the cell. It is a peripheral membrane ATPase involved in plasmid partitioning.

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References

  1. ↑ De Boer PA, Crossley RE, Rothfield LI (1989). "A division inhibitor and a topological specificity factor coded for by the minicell locus determine proper placement of the division septum in E. coli". Cell. 56 (4): 641–649. doi:10.1016/0092-8674(89)90586-2. PMID   2645057. S2CID   7650379.
  2. ↑ Adler HI, Fisher WD, Cohen A, Hardigree AA; Fisher; Cohen; Hardigree (1967). "Miniature Escherichia coli Cells Deficient in DNA". PNAS. 57 (2): 321–326. Bibcode:1967PNAS...57..321A. doi: 10.1073/pnas.57.2.321 . PMC   335508 . PMID   16591472.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  3. ↑ Weart RB, Levin PA (2003). "Growth Rate-Dependent Regulation of Medial FtsZ Ring Formation". J Bacteriol. 185 (9): 2826–2834. doi:10.1128/JB.185.9.2826-2834.2003. PMC   154409 . PMID   12700262.
  4. ↑ Hu Z, Gogol EP, Lutkenhaus J (2002). "Dynamic assembly of MinD on phospholipid vesicles regulated by ATP and MinE". Proc Natl Acad Sci USA. 99 (10): 6761–6766. Bibcode:2002PNAS...99.6761H. doi: 10.1073/pnas.102059099 . PMC   124476 . PMID   11983867.
  5. ↑ Huang KC, Meir Y, Wingreen NS (2003). "Dynamic structures in Escherichia coli: Spontaneous formation of MinE rings and MinD polar zones". Proc Natl Acad Sci USA. 100 (22): 12724–12728. Bibcode:2003PNAS..10012724H. doi: 10.1073/pnas.2135445100 . PMC   240685 . PMID   14569005.
  6. ↑ Hu Z, Saez C, Lutkenhaus J (2003). "Recruitment of MinC, an Inhibitor of Z-Ring Formation, to the Membrane in Escherichia coli: Role of MinD and MinE". J Bacteriol. 185 (1): 196–203. doi:10.1128/JB.185.1.196-203.2003. PMC   141945 . PMID   12486056.
  7. ↑ Hu Z, Lutkenhaus J (2001). "Topological regulation of cell division in E. coli: spatiotemporal oscillation of MinD requires stimulation of its ATPase by MinE and phospholipid". Mol Cell. 7 (6): 1337–1343. doi: 10.1016/S1097-2765(01)00273-8 . PMID   11430835.
  8. ↑ Dajkovic A, Lutkenhaus J (2006). "Z Ring as Executor of Bacterial Cell Division". J Mol Micro Bio. 11 (3–5): 140–151. doi:10.1159/000094050. PMID   16983191. S2CID   10043376.
  9. ↑ Marston AL, Thomaides HB, Edwards DH, Sharpe ME, Errington J (1998). "Polar localization of the MinD protein of Bacillus subtilis and its role in selection of the mid-cell division site". Genes Dev. 12 (21): 3419–3430. doi:10.1101/gad.12.21.3419. PMC   317235 . PMID   9808628.
  10. ↑ Loose, Martin; Fischer-Friedrich, Elisabeth; Ries, Jonas; Kruse, Karsten; Schwille, Petra (2008-05-09). "Spatial regulators for bacterial cell division self-organize into surface waves in vitro". Science. 320 (5877): 789–792. Bibcode:2008Sci...320..789L. doi:10.1126/science.1154413. ISSN   1095-9203. PMID   18467587. S2CID   27134918.
  11. ↑ Vecchiarelli, Anthony G.; Li, Min; Mizuuchi, Michiyo; Mizuuchi, Kiyoshi (2014-08-01). "Differential affinities of MinD and MinE to anionic phospholipid influence Min patterning dynamics in vitro". Molecular Microbiology. 93 (3): 453–463. doi:10.1111/mmi.12669. ISSN   1365-2958. PMC   4116444 . PMID   24930948.
  12. ↑ Zieske, Katja; Schwille, Petra (2014-01-01). "Reconstitution of self-organizing protein gradients as spatial cues in cell-free systems". eLife. 3. doi: 10.7554/eLife.03949 . ISSN   2050-084X. PMC   4215534 . PMID   25271375.
  13. ↑ Loose, Martin; Fischer-Friedrich, Elisabeth; Ries, Jonas; Kruse, Karsten; Schwille, Petra (2008-05-09). "Spatial regulators for bacterial cell division self-organize into surface waves in vitro". Science. 320 (5877): 789–792. Bibcode:2008Sci...320..789L. doi:10.1126/science.1154413. ISSN   1095-9203. PMID   18467587. S2CID   27134918.
  14. ↑ Loose, Martin; Fischer-Friedrich, Elisabeth; Herold, Christoph; Kruse, Karsten; Schwille, Petra (2011-05-09). "Min protein patterns emerge from rapid rebinding and membrane interaction of MinE". Nat Struct Mol Biol. 18 (5): 577–83. doi:10.1038/nsmb.2037. PMID   21516096. S2CID   30014235.
  15. ↑ Ivanov, V.; Mizuuchi, K. (2010-03-08). "Multiple modes of interconverting dynamic pattern formation by bacterial cell division proteins". Proceedings of the National Academy of Sciences. 107 (18): 8071–8078. doi: 10.1073/pnas.0911036107 . ISSN   0027-8424. PMC   2889524 . PMID   20212106.
  16. ↑ Vecchiarelli, Anthony G.; Li, Min; Mizuuchi, Michiyo; Hwang, Ling Chin; Seol, Yeonee; Neuman, Keir C.; Mizuuchi, Kiyoshi (2016-03-15). "Membrane-bound MinDE complex acts as a toggle switch that drives Min oscillation coupled to cytoplasmic depletion of MinD". Proceedings of the National Academy of Sciences of the United States of America. 113 (11): E1479–1488. Bibcode:2016PNAS..113E1479V. doi: 10.1073/pnas.1600644113 . ISSN   1091-6490. PMC   4801307 . PMID   26884160.
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