Bacterial cytokinesis is mediated by the septal ring, a cytoskeletal-like organelle that is associated with the cytoplasmic membrane at the site of division. The long-term goals of the proposed research are to understand at a molecular level: i) The composition and architecture of the organelle, ii) How the ring assembles from its different components, iii) How the proper site for its assembly is determined, and iv) How the ring drives cell constriction. In E.coli, the organelle consists of at least nine essential division proteins that co-assemble in a specific order to form the mature structure. The first recognized step in the formation pathway is self-assembly of the tubulin-like GTPase FtsZ on the membrane. FtsZ polymers are bound by the ZipA and FtsA proteins, resulting in a tripartite intermediate that is required for recruitment of the other components. Septal ring assembly in the cell is controlled by MinC, an inhibitor of FtsZ polymerization. The activity of MinC, in turn, is controlled by the MinD and MinE proteins. The latter two cause MinC to rapidly oscillate from pole-to-pole, forcing FtsZ assembly to the middle of the cell. Evidence indicates that MinD, in addition to driving oscillation of MinC, also specifically targets the division inhibitor to early septal ring intermediates, which are misplaced and destined for destruction. The DicB protein of bacteriophage Kim is also a potent stimulator of MinC activity, and appears to target MinC to its substratein a similar manner. It is proposed to elucidate the mechanisms whereby MinD and DicB help to target MinC activity, and to characterize the composition of the target(s). For this and other purposes it is proposed to develop in vitro systems wherein the properties of early septal ring complexes may be studied in their 'natural' membrane-associated state. Evidence further indicates that, in addition to the known division factors, a number of components are missing from the current septal ring model. Some of these must also be early components and be responsible for the onset of septal murein synthesis. It is proposed to identify additional septal ring components by determining the cellular distribution of several good candidates.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057059-08
Application #
6849278
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Deatherage, James F
Project Start
1998-02-01
Project End
2007-01-31
Budget Start
2005-02-01
Budget End
2006-01-31
Support Year
8
Fiscal Year
2005
Total Cost
$298,350
Indirect Cost
Name
Case Western Reserve University
Department
Biochemistry
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
de Boer, Piet A J (2016) Classic Spotlight: Cellular Sites of Peptidoglycan Synthesis Revealed. J Bacteriol 198:1795
de Boer, Piet A J (2016) Bacterial physiology: Life minus Z. Nat Microbiol 1:16121
de Boer, Piet A J (2016) Classic Spotlight: Discovery of ftsZ. J Bacteriol 198:1184
de Boer, Piet A J (2016) Classic Spotlight: Staying in Shape and Discovery of the mrdAB and mreBCD Operons. J Bacteriol 198:1479
Liu, Bing; Persons, Logan; Lee, Lynda et al. (2015) Roles for both FtsA and the FtsBLQ subcomplex in FtsN-stimulated cell constriction in Escherichia coli. Mol Microbiol 95:945-70
Heidari Torkabadi, Hossein; Bethel, Christopher R; Papp-Wallace, Krisztina M et al. (2014) Following drug uptake and reactions inside Escherichia coli cells by Raman microspectroscopy. Biochemistry 53:4113-21
Ouellette, Scot P; Rueden, Kelsey J; Gauliard, Emilie et al. (2014) Analysis of MreB interactors in Chlamydia reveals a RodZ homolog but fails to detect an interaction with MraY. Front Microbiol 5:279
Salje, Jeanne; van den Ent, Fusinita; de Boer, Piet et al. (2011) Direct membrane binding by bacterial actin MreB. Mol Cell 43:478-87
Cho, Hongbaek; McManus, Heather R; Dove, Simon L et al. (2011) Nucleoid occlusion factor SlmA is a DNA-activated FtsZ polymerization antagonist. Proc Natl Acad Sci U S A 108:3773-8
Hale, Cynthia A; Shiomi, Daisuke; Liu, Bing et al. (2011) Identification of Escherichia coli ZapC (YcbW) as a component of the division apparatus that binds and bundles FtsZ polymers. J Bacteriol 193:1393-404

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