FtsZ dynamics in bacterial division: What, how, and why?

Abstract

Bacterial cell division is orchestrated by the divisome, a protein complex centered on the tubulin homolog FtsZ. FtsZ polymerizes into a dynamic ring that defines the division site, recruits downstream proteins, and directs peptidoglycan synthesis to drive constriction. Recent studies have documented treadmilling of FtsZ polymer clusters both in cells and in vitro. Emerging evidence suggests that FtsZ dynamics are regulated largely by intrinsic properties of FtsZ itself and by the membrane anchoring protein FtsA. Although FtsZ dynamics are broadly required for Z-ring assembly, their role(s) during constriction may vary among bacterial species. These recent advances set the stage for future studies to investigate how FtsZ dynamics are physically and/or functionally coupled to peptidoglycan metabolic enzymes to direct efficient division.

Keywords: Bacteria; Cell division; Cell wall; Cytokinesis; Cytoskeleton; FtsZ; Peptidoglycan; Treadmilling.

Figure 1:. A host of localization systems contribute to Z-ring assembly throughout the cell cycle.

Early in the cell cycle, FtsZ (blue haze) is rapidly redistributed from the poles throughout the cell. Prior to the subsequent division event as the chromosome (bronze line) is being replicated, the division site is selected by spatially regulated polymerization of FtsZ into a mid-cell ring. Depending on the organism, negative (green arrows) Z-ring regulators (Min system or MipZ) promote disassembly of FtsZ polymers near the poles, or positive (purple arrows) Z-ring regulators (MapZ or PomZ) promote local mid-cell assembly of FtsZ polymers (blue gradient lines). Z-ring assembly and condensation are further facilitated by association with membrane anchors (red spheres) and Z-binding proteins (orange ellipses), e.g. ZapA, at mid-cell.

Figure 2:. FtsZ treadmilling on SLBs depends on membrane association, GTPase activity, and proper lateral interactions.

Model for polymer behavior (left) and representative experimental view (right) of each scenario are represented. A. Treadmilling of E. coli FtsZ (blue gradient arrow and lines) occurs on SLBs when FtsZ can bind (dark blue) and hydrolyze (light blue) GTP and the local concentration of FtsZ at the membrane, facilitated by a membrane anchor (red spheres) or a membrane targeting sequence (not shown), is sufficient to allow for both polymerization and depolymerization. Treadmilling FtsZ is typically observed in either single clusters or chiral swirls, from each of which treadmilling rates can be determined. B. E. coli FtsZ forms asters or bundles/mesh-like structures under conditions of high E. coli ZipA or high free Mg²⁺ concentrations, respectively. Treadmilling has not been observed under these conditions, although polymers are still dynamic. C. C. crescentus FtsZ fused to a membrane targeting sequence (FtsZ-MTS) forms small dynamic clusters that do not appear to move by treadmilling under conditions tested thus far. D. C. crescentus FtsZ lacking its C-terminal linker (ΔCTL-MTS) forms stable, mesh-like structures that are more stable compared to WT.

Figure 3:. The relationships between FtsZ treadmilling and PG enzyme complex movement and activity vary across organisms.

A. E. coli bears both fast, inactive (dark green) and slow, active (light green) moving PG enzyme populations, and FtsZ treadmilling rates correlate with the former. B. B. subtilis inactive and active PG enzyme complexes comprise a single population of moving molecules that correlates with and depends on FtsZ treadmilling. C. S. pneumoniae inactive and active PG enzyme complexes comprise a single population of moving molecules that does not correlate with or depend on FtsZ treadmilling. D. S. aureus has a moving population of PG enzyme complexes and treadmilling FtsZ, but the rates of each have yet to be determined.