EzrA prevents aberrant cell division by modulating assembly of the cytoskeletal protein FtsZ

Haeusser, Daniel P.; Schwartz, Richard S.; Smith, Alison M.; Oates, Michelle Erin; Levin, Petra Anne

doi:10.1111/j.1365-2958.2004.04016.x

Cited by 115 publications

(157 citation statements)

References 57 publications

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“…We also quantified the levels of endogenous FtsZ in the same extract (Fig. S3 C and E), and found 4,200 molecules per cell, similarly to published data that indicates that B. subtilis contains at least 5,000 molecules of FtsZ per cell when grown in rich medium (36,37). This result suggests that a ratio of MciZ to FtsZ of less than 1:10 is enough to completely block Z-ring formation and cell division in vivo.…”

Section: Substoichiometric Mciz Inhibits Z-ring Formation In Vivosupporting

confidence: 65%

FtsZ filament capping by MciZ, a developmental regulator of bacterial division

Bisson‐Filho

Discola

Castellen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Cytoskeletal structures are dynamically remodeled with the aid of regulatory proteins. FtsZ (filamentation temperature-sensitive Z) is the bacterial homolog of tubulin that polymerizes into rings localized to cell-division sites, and the constriction of these rings drives cytokinesis. Here we investigate the mechanism by which the Bacillus subtilis cell-division inhibitor, MciZ (mother cell inhibitor of FtsZ), blocks assembly of FtsZ. The X-ray crystal structure reveals that MciZ binds to the C-terminal polymerization interface of FtsZ, the equivalent of the minus end of tubulin. Using in vivo and in vitro assays and microscopy, we show that MciZ, at substoichiometric levels to FtsZ, causes shortening of protofilaments and blocks the assembly of higher-order FtsZ structures. The findings demonstrate an unanticipated capping-based regulatory mechanism for FtsZ.T he discovery that bacteria have actin-, tubulin-, and intermediate filament-like proteins demonstrated that the cytoskeleton is an ancient invention, predating the divergence between prokaryotes and eukaryotes (1). The GTPase FtsZ (filamentation temperature-sensitive Z) was the first prokaryotic protein to be recognized as a cytoskeletal element (2, 3). FtsZ is a tubulin-like protein, which is widely conserved in bacteria and the main component of the bacterial cytokinesis machine, or "divisome." FtsZ self-assembles into single-stranded protofilaments and these associate further inside cells to form a superstructure known as the Z ring (4, 5). FtsZ alone can generate a constriction force to initiate division (6). The Z ring also provides a scaffold onto which several other components of the divisome-mostly cell wall synthesizing enzymes-are recruited and oriented so as to build the division septum, a cross-wall separating a progenitor cell into two isogenic daughter cells (7).FtsZ and tubulin share several essential properties: their assembly is cooperative, stimulated by GTP, and leads to GTP hydrolysis; they form dynamic polymers whose turnover is dependent on nucleotide hydrolysis (8); they use essentially the same bond for polymer formation (9); and recent evidence indicates that they undergo similar allosteric transitions upon polymerization (10, 11). Not surprisingly, however, the functional specialization of these proteins led to some significant differences between them, the most prominent being that FtsZ exists as single protofilaments, whereas tubulin always adopts a multifilament tubular structure. This difference in their higherorder structure implies that the reactions that lead to cooperativity and subunit turnover are likely different. It has also represented a significant technical challenge for the study of FtsZ. Because FtsZ filaments are smaller than the resolution of optical microscopy, so far it has been impossible to determine essential properties associated with its dynamic behavior.Similarly to actin filaments and microtubules, the assembly of FtsZ protofilaments into a Z ring is regulated by a number of proteins that bind directly...

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Section: Substoichiometric Mciz Inhibits Z-ring Formation In Vivosupporting

confidence: 65%

FtsZ filament capping by MciZ, a developmental regulator of bacterial division

Bisson‐Filho

Discola

Castellen

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…The topology of ZipA is unusual, with its N terminus in the cytoplasmic membrane and its C terminus, which is sufficient for the bundling activity, in the cytoplasm. A protein that has a similar topology, known as EzrA, is present in B. subtilis and other Gram-positive bacteria; EzrA, however, is a negative regulator of Z-ring assembly and inhibits FtsZ polymerization in vitro 74,75 . As ZipA and EzrA bind directly to FtsZ, they must therefore regulate FtsZ assembly at the membrane.…”

Section: Other Regulators Of Z-ring Assemblymentioning

confidence: 99%

FtsZ and the division of prokaryotic cells and organelles

Margolin

2005

Nat Rev Mol Cell Biol

558

484

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Binary fission of many prokaryotes as well as some eukaryotic organelles depends on the FtsZ protein, which self-assembles into a membrane-associated ring structure early in the division process. FtsZ is homologous to tubulin, the building block of the microtubule cytoskeleton in eukaryotes. Recent advances in genomics and cell-imaging techniques have paved the way for the remarkable progress in our understanding of fission in bacteria and organelles.Duplication of cells occurs by the division of a mother cell into two daughter cells. This process, known as cytokinesis, provides the force to split cells and is spatially regulated to faithfully partition the genetic material. The cytoskeleton has a crucial role in cytokinesis. In animal and fungal cells, a medial ring of actin and myosin, helped by other proteins, contracts to divide the cell. Plant cells use a cell plate, and are guided by actin filaments and microtubules. Prokaryotes, which include bacteria and archaea, possess homologues of eukaryotic cytoskeletal proteins. Most prokaryotes use a tubulin homologue, a protein known as FtsZ, to divide. Eukaryotic organelles such as chloroplasts and mitochondria evolved from bacteria, and all chloroplasts and some mitochondria use FtsZ to divide.FtsZ is thought to be the first protein to localize to the site of future division in bacteria 1 , and it assembles into what is known as the Z ring (FIG. 1). In Escherichia coli, the Z ring recruits at least ten other proteins, all of which are required for the progression and completion of cytokinesis 2 , as will be discussed below. Whereas the cytokinetic apparatus in eukaryotic cells and even organelles can be observed directly in stained thin sections by transmission electron microscopy, the Z ring and its associated factors are not detectable by these methods. This is probably because the protein machinery is largely membrane bound and resides in a densely populated cytoplasmic environment. However, the development of green fluorescent protein (GFP) fusion and improved immunofluorescence techniques over the past 10 years have been crucial in allowing the first direct visualization of many cellular components and their dynamics. For example, using GFP fusions, the dynamics of the Z ring and other components of the cell-division protein machinery can now be visualized in living bacterial cells. The combination of these new cytological tools with genomics and the Competing interests statementThe author declares no competing financial interests. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript already powerful genetics of several model systems have spurred rapid progress in our understanding of the molecular cell biology of bacteria and eukaryotic organelles. This review will discuss how the recent revolutions in genomics and cell biology have provided new evolutionary and mechanistic insights into how bacterial cells and organelles divide. The FtsZ family of proteins Conservation of FtsZFtsZ is a highly conserved protein ...

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“…Also EzrA localizes to the Z ring early, along with FtsA and ZapA (54). On the other hand EzrA is best characterized as a negative regulator of Z rings (66,96), so its role as a tether is not intuitive.…”

Section: Tethering Ftsz To the Membranementioning

confidence: 99%

FtsZ in Bacterial Cytokinesis: Cytoskeleton and Force Generator All in One

Erickson

Anderson

Osawa

2010

Microbiol Mol Biol Rev

557

752

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SUMMARY FtsZ, a bacterial homolog of tubulin, is well established as forming the cytoskeletal framework for the cytokinetic ring. Recent work has shown that purified FtsZ, in the absence of any other division proteins, can assemble Z rings when incorporated inside tubular liposomes. Moreover, these artificial Z rings can generate a constriction force, demonstrating that FtsZ is its own force generator. Here we review light microscope observations of how Z rings assemble in bacteria. Assembly begins with long-pitch helices that condense into the Z ring. Once formed, the Z ring can transition to short-pitch helices that are suggestive of its structure. FtsZ assembles in vitro into short protofilaments that are ∼30 subunits long. We present models for how these protofilaments might be further assembled into the Z ring. We discuss recent experiments on assembly dynamics of FtsZ in vitro, with particular attention to how two regulatory proteins, SulA and MinC, inhibit assembly. Recent efforts to develop antibacterial drugs that target FtsZ are reviewed. Finally, we discuss evidence of how FtsZ generates a constriction force: by protofilament bending into a curved conformation.

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EzrA prevents aberrant cell division by modulating assembly of the cytoskeletal protein FtsZ

Cited by 115 publications

References 57 publications

FtsZ filament capping by MciZ, a developmental regulator of bacterial division

FtsZ filament capping by MciZ, a developmental regulator of bacterial division

FtsZ and the division of prokaryotic cells and organelles

FtsZ in Bacterial Cytokinesis: Cytoskeleton and Force Generator All in One

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