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FtsA mutants impaired for self-interaction bypass ZipA suggesting a model in which FtsA's self-interaction competes with its ability to recruit downstream division proteins.
Mol Microbiol. 2012 Jan; 83(1):151-67
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21 Mar 2012
New Finding
DOI: 10.3410/f.14187965.15695065
This paper from Joe Lutkenhaus' lab presents an exciting new model for how FtsA facilitates bacterial cell division.
FtsA, a distant homolog of actin, is a key component of the septal ring that mediates cytokinesis. One function of FtsA is to tether the FtsZ ring to the cytoplasmic membrane. This function...Continue reading
FtsA, a distant homolog of actin, is a key component of the septal ring that mediates cytokinesis. One function of FtsA is to tether the FtsZ ring to the cytoplasmic membrane. This function...Continue reading
This paper from Joe Lutkenhaus' lab presents an exciting new model for how FtsA facilitates bacterial cell division.
FtsA, a distant homolog of actin, is a key component of the septal ring that mediates cytokinesis. One function of FtsA is to tether the FtsZ ring to the cytoplasmic membrane. This function is reasonably well understood because FtsA binds directly to both FtsZ and the membrane. Another function of FtsA is to recruit a host of additional division proteins to the septal ring. These proteins are often referred to as "late" because they do not arrive at the septal ring until well after "early" proteins such as FtsZ and FtsA. Several groups have published evidence that FtsA interacts with various late proteins, which would in principle explain the mechanism of recruitment, but there is a considerable lag between arrival of FtsA and recruitment of the late proteins {1}. This lag casts some doubt on the direct recruitment model.
Working in Escherichia coli, Pichoff et al. isolated a set of ftsA mutants that point to a potential resolution of this paradox. The key observation is that the ftsA mutants are defective in self-association but better at promoting cell division. For example, they bypass the normal requirement for an early protein named ZipA and they are less toxic than wild type when overproduced.
These and other findings in the paper lead Pichoff et al. to propose that FtsA assembles into the septal ring as a multimer but cannot recruit the late proteins until remodeling converts FtsA to a monomer, exposing a site (domain 1c) that interacts with one or more late division proteins. Pichoff et al. further suggest that ZipA plays a key role in converting FtsA from a multimeric to a monomeric state.
In this context, it is also interesting to note a recent report from the Margolin lab showing that the cytoplasmic domain of the late protein FtsN interacts with domain 1c of FtsA {2}.
FtsA, a distant homolog of actin, is a key component of the septal ring that mediates cytokinesis. One function of FtsA is to tether the FtsZ ring to the cytoplasmic membrane. This function is reasonably well understood because FtsA binds directly to both FtsZ and the membrane. Another function of FtsA is to recruit a host of additional division proteins to the septal ring. These proteins are often referred to as "late" because they do not arrive at the septal ring until well after "early" proteins such as FtsZ and FtsA. Several groups have published evidence that FtsA interacts with various late proteins, which would in principle explain the mechanism of recruitment, but there is a considerable lag between arrival of FtsA and recruitment of the late proteins {1}. This lag casts some doubt on the direct recruitment model.
Working in Escherichia coli, Pichoff et al. isolated a set of ftsA mutants that point to a potential resolution of this paradox. The key observation is that the ftsA mutants are defective in self-association but better at promoting cell division. For example, they bypass the normal requirement for an early protein named ZipA and they are less toxic than wild type when overproduced.
These and other findings in the paper lead Pichoff et al. to propose that FtsA assembles into the septal ring as a multimer but cannot recruit the late proteins until remodeling converts FtsA to a monomer, exposing a site (domain 1c) that interacts with one or more late division proteins. Pichoff et al. further suggest that ZipA plays a key role in converting FtsA from a multimeric to a monomeric state.
In this context, it is also interesting to note a recent report from the Margolin lab showing that the cytoplasmic domain of the late protein FtsN interacts with domain 1c of FtsA {2}.
References
1.
Maturation of the Escherichia coli divisome occurs in two steps.
Mol Microbiol 2005 Mar; 6(55):1631-45
PMID: 15752189
2.
The Early Divisome Protein FtsA Interacts Directly through Its 1c Subdomain with the Cytoplasmic Domain of the Late Divisome Protein FtsN.
J Bacteriol 2012 Apr; 8(194):1989-2000
PMID: 22328664
Disclosures
None declared
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Weiss D: F1000Prime Recommendation of [Pichoff S et al., Mol Microbiol 2012, 83(1):151-67]. In F1000Prime, 21 Mar 2012; DOI: 10.3410/f.14187965.15695065. F1000Prime.com/14187965#eval15695065
25 Apr 2012
New Finding
DOI: 10.3410/f.14187965.15779578
The actin homolog FtsA is an essential cell division protein in Escherichia coli, where it binds FtsZ and tethers it to the membrane, and recruits downstream proteins to the Z ring. ZipA, another membrane tether for FtsZ, is also essential. In 2003, Geissler et al. discovered a gain-of-function mutant...Continue reading
The actin homolog FtsA is an essential cell division protein in Escherichia coli, where it binds FtsZ and tethers it to the membrane, and recruits downstream proteins to the Z ring. ZipA, another membrane tether for FtsZ, is also essential. In 2003, Geissler et al. discovered a gain-of-function mutant of FtsA called FtsA* that bypassed the requirement for ZipA {1}. Now Pichoff et al. have found about 20 additional mutants of FtsA that can bypass the requirement for ZipA, and have made a surprising correlation with self-interaction.
In addition to bypassing the requirement for ZipA, most of these FtsA* mutants can complement a temperature-sensitive FtsA allele at lower concentrations than wild type FtsA, suggesting that they are some kind of super FtsA. But the surprising correlation is that most of these mutants inhibit the self-interaction of FtsA. One might have expected that mutations blocking a natural self-association would be deleterious.
This expected result, a deleterious effect of FtsA mutants blocked for self-association, was in fact found for Bacillus subtilis {2}. In B. subtilis FtsA is not essential, but deletion leads to division defects and filamentous cells. Szwedziak et al. showed that B. subtilis FtsA can assemble into actin-like filaments, and found that mutants that blocked this assembly can only partially rescue the division defects of a temperature-sensitive FtsA {2}. Of course self-assembly of FtsA must serve a function even in E. coli, but it may be subtle. It appears that in the absence of ZipA, monomeric FtsA is better than oligomers. The mechanism awaits further study.
In addition to bypassing the requirement for ZipA, most of these FtsA* mutants can complement a temperature-sensitive FtsA allele at lower concentrations than wild type FtsA, suggesting that they are some kind of super FtsA. But the surprising correlation is that most of these mutants inhibit the self-interaction of FtsA. One might have expected that mutations blocking a natural self-association would be deleterious.
This expected result, a deleterious effect of FtsA mutants blocked for self-association, was in fact found for Bacillus subtilis {2}. In B. subtilis FtsA is not essential, but deletion leads to division defects and filamentous cells. Szwedziak et al. showed that B. subtilis FtsA can assemble into actin-like filaments, and found that mutants that blocked this assembly can only partially rescue the division defects of a temperature-sensitive FtsA {2}. Of course self-assembly of FtsA must serve a function even in E. coli, but it may be subtle. It appears that in the absence of ZipA, monomeric FtsA is better than oligomers. The mechanism awaits further study.
References
1.
A gain-of-function mutation in ftsA bypasses the requirement for the essential cell division gene zipA in Escherichia coli.
Proc Natl Acad Sci U S A 2003 Apr 1; 100(7): 4197-202
PMID: 12634424
DOI: 10.1073/pnas.0635003100
2.
Disclosures
None declared
Erickson H: F1000Prime Recommendation of [Pichoff S et al., Mol Microbiol 2012, 83(1):151-67]. In F1000Prime, 25 Apr 2012; DOI: 10.3410/f.14187965.15779578. F1000Prime.com/14187965#eval15779578
F1000Prime Recommendations, Dissents and Comments for [Pichoff S et al., Mol Microbiol 2012, 83(1):151-67]. In F1000Prime, 19 May 2013; F1000Prime.com/14187965
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Z-ring assembly requires polymers of the tubulin homologue FtsZ to be tethered to the membrane. Although either ZipA or FtsA is sufficient to do this, both of these are required for recruitment of downstream proteins to form a functional cytokinetic ring. Gain of function mutations in ftsA, such as ftsA* (ftsA-R286W), bypass the requirement for ZipA suggesting that this atypical, well-conserved, actin homologue has a more critical role in Z-ring function. FtsA forms multimers both in vitro and in vivo, but little is known about the role of FtsA polymerization. In this study we identify FtsA mutants impaired for self-interaction. Such mutants are able to support Z-ring assembly and are also able to bypass the requirement for ZipA. These mutants, including FtsA*, have reduced ability to self-interact but interact normally with FtsZ and are less toxic if overexpressed. These results do not support a model in which FtsA monomers antagonize FtsZ polymers. Instead, we propose a new model in which FtsA self-interaction competes with its ability to recruit downstream proteins. In this model FtsA self-interaction at the Z ring is antagonized by ZipA, allowing unpolymerized FtsA to recruit downstream proteins such as FtsN.
© 2011 Blackwell Publishing Ltd.
DOI: 10.1111/j.1365-2958.2011.07923.x
PMID: 22111832
