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

Pichoff, Sébastien; Shen, Bang; Sullivan, Bradley P.; Lutkenhaus, Joe

doi:10.1111/j.1365-2958.2011.07923.x

Cited by 113 publications

(196 citation statements)

References 49 publications

(129 reference statements)

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“…Although it is unclear how this interaction leads to recruitment of downstream division proteins, the fact that all FtsA mutants that bypass ZipA also bypass FtsEX suggests that FtsEX, like ZipA, modulates FtsA's ability to recruit downstream divisome proteins. Because most of the FtsA mutants that bypass ZipA are impaired for self-interaction, we proposed previously that ZipA acts by antagonizing FtsA polymerization although the mechanism is unclear (20). Here, we propose that FtsEX also does this, but by directly interacting with FtsA.…”

Section: Discussionmentioning

confidence: 59%

“…Second, FtsA has been reported to interact with many downstream division proteins (22), including FtsN (23)(24)(25). Importantly, FtsA mutants impaired for self-interaction and overexpression of FtsN bypass ZipA, supporting a model in which FtsA monomers recruit downstream division proteins to the Z ring (20,25). In this model the essential role of ZipA in recruitment is to antagonize FtsA polymerization.…”

mentioning

confidence: 80%

“…This difference may be because of a difference in the strength of the mutation. FtsA R286W and FtsA L204A appear to be stronger because they bypass ZipA at a lower level of expression than FtsA E124A and FtsA I143L (20). In addition, the stronger ftsB E56A mutation could fully rescue FtsA R63H or FtsA G366D at both 37°C and 42°C, whereas the weaker ftsB D59H mutation only fully rescued at 42°C (SI Appendix, Fig.…”

Section: Interaction Between Ftsa and Ftsx Is Important For Divisomementioning

confidence: 91%

“…We chose two ftsA mutations that have been reported to require less FtsN for division (ftsA E124A and ftsA I143L , because they bypass the function of E FtsN) as well as several mutations that have been reported to bypass ZipA (ftsA M167I , ftsA R177C , ftsA L204 , and ftsA R286W ) (20,24,38). The mutations in the former class were considered unique because they affect residues in the IC domain of FtsA (SI Appendix , Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Accumulating evidence indicates that FtsA, an actinrelated protein, plays a critical role. First, other than FtsA and FtsZ, the early divisome proteins (ZipA, FtsEX, EnvC, and the Zaps) can be deleted under certain conditions and the divisome can still assemble and function (7,8,(19)(20)(21). Second, FtsA has been reported to interact with many downstream division proteins (22), including FtsN (23)(24)(25).…”

mentioning

confidence: 99%

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FtsEX acts on FtsA to regulate divisome assembly and activity

Pichoff

Lutkenhaus

2016

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

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Bacterial cell division is driven by the divisome, a ring-shaped protein complex organized by the bacterial tubulin homolog FtsZ. Although most of the division proteins in Escherichia coli have been identified, how they assemble into the divisome and synthesize the septum remains poorly understood. Recent studies suggest that the bacterial actin homolog FtsA plays a critical role in divisome assembly and acts synergistically with the FtsQLB complex to regulate the activity of the divisome. FtsEX, an ATP-binding cassette transporter-like complex, is also necessary for divisome assembly and inhibits division when its ATPase activity is inactivated. However, its role in division is not clear. Here, we find that FtsEX acts on FtsA to regulate both divisome assembly and activity. FtsX interacts with FtsA and this interaction is required for divisome assembly and inhibition of divisome function by ATPase mutants of FtsEX. Our results suggest that FtsEX antagonizes FtsA polymerization to promote divisome assembly and the ATPase mutants of FtsEX block divisome activity by locking FtsA in the inactive form or preventing FtsA from communicating with other divisome proteins. Because FtsEX is known to govern cell wall hydrolysis at the septum, our findings indicate that FtsEX acts on FtsA to promote divisome assembly and to coordinate cell wall synthesis and hydrolysis at the septum. Furthermore, our study provides evidence that FtsA mutants impaired for self-interaction are favored for division, and FtsW plays a critical role in divisome activation in addition to the FtsQLB complex.

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Section: Discussionmentioning

confidence: 59%

mentioning

confidence: 80%

Section: Interaction Between Ftsa and Ftsx Is Important For Divisomementioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

FtsEX acts on FtsA to regulate divisome assembly and activity

Pichoff

Lutkenhaus

2016

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

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203

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Gene‐Directed FtsZ Ring Assembly Generates Constricted Liposomes with Stable Membrane Necks

Godino

Danelon

2023

Advanced Biology

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vesicles. With a limited number of division factors compared to eukaryotes, the Escherichia coli divisome has been at the center of numerous efforts attempting to split liposomes. [5][6][7][8][9][10][11][12] In vivo, a contractile ring composed of FtsZ, FtsA, and ZipA is formed at midcell. [13,14] FtsZ is a bacterial homologue of tubulin [15][16][17] that polymerizes into self-interacting filaments when bound to GTP. [18][19][20][21] FtsZ lacks a membrane targeting domain, and it is anchored to the cytoplasmic bilayer by FtsA and ZipA.In vitro reconstruction of FtsZ polymers, [15,22] FtsA and ZipA [23] in model membranes has contributed to elucidate the self-organization and dynamics of the E. coli division proteins. In 2008, Osawa and colleagues suggested that Z-rings could generate constriction forces within tubular liposomes in the absence of motor proteins. [5] In this work, FtsZ-mts (a chimeric FtsZ with a membrane targeting sequence fused to the C terminus) caused membrane invagination, though full constriction was not achieved. [5] The authors proposed that the conformational change of FtsZ from straight to curved filaments acts as the driving force. In a follow-up study, the same group claimed that the Z-ring stimulates membrane constriction in giant liposomes to the point of septation. [7] The use of FtsA*, a gain-of-function mutant of FtsA, [24] was required to achieve complete scission, as such division events were not observed with FtsZ-mts. Szwedziak and colleagues showed that purified FtsZ and FtsA from Thermotoga maritima form continuous filament rings encircling the membrane on the inside of small unilamellar vesicles, generating constriction sites but evidences of membrane abscission were not presented. [9] The authors proposed a scenario, where the sliding and shortening of overlapping FtsZ filaments constitute the main force generator. [9] Interestingly, Ramirez Diaz and colleagues reported that FtsZ filaments do not have a single curvature, [25] and that their intrinsic helical structure drives liposome deformation via torsional stress, a mechanism that is reliant on GTP hydrolysis. [12] With the aim to recapitulate a functional Z-ring from gene-encoded proteins in liposomes, our group has demonstrated that ring-like cytoskeletal structures led to membrane constriction into narrow necks connecting budding vesicles, [11] a phenotype that differs from that observed in previous studies by the more pronounced pinching of the liposome membrane. Although no division events could unambiguously be detected, our experimental design was not directed toward addressing Mimicking bacterial cell division in well-defined cell-free systems has the potential to elucidate the minimal set of proteins required for cytoskeletal formation, membrane constriction, and final abscission. Membrane-anchored FtsZ polymers are often regarded as a sufficient system to realize this chain of events. By using purified FtsZ and its membrane-binding protein FtsA or the gain-of-function mutant FtsA* expressed in PURE (Protein syn...

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Bacterial cytokinesis: From Z ring to divisome

Lutkenhaus¹,

Pichoff²,

Du³

2012

Cytoskeleton

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Ancestral homologues of the major eukaryotic cytoskeletal families, tubulin and actin, play critical roles in cytokinesis of bacterial cells. FtsZ is the ancestral homologue of tubulin and assembles into the Z ring that determines the division plane. FtsA is an ancestral homologue of actin and is involved in coordinating cell wall synthesis during cytokinesis. FtsA assists in the formation of the Z ring and also has a critical role in recruiting downstream division proteins to the Z ring to generate the divisome that divides the cell. Spatial regulation of cytokinesis occurs at the stage of Z ring assembly and regulation of cell size occurs at this stage or during Z ring maturation.

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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

Cited by 113 publications

References 49 publications

FtsEX acts on FtsA to regulate divisome assembly and activity

FtsEX acts on FtsA to regulate divisome assembly and activity

Gene‐Directed FtsZ Ring Assembly Generates Constricted Liposomes with Stable Membrane Necks

Bacterial cytokinesis: From Z ring to divisome

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