Bacterial cytokinesis: From Z ring to divisome

Abstract

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, a member of the actin family, 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.

Fig. 1

Structures of FtsZ and tubulin. The residues that are most conserved in FtsZ (PDB 2VAW) and tubulin (PDB 1TUB) are involved in the binding and hydrolyzing of GTP and include the synergy loop (NxDxx[D/E] (residues in caps and colored magenta) and the signature loop (GGGTG[T/S]G, colored blue) that binds the phosphates. The synergy loop in β-tubulin does not induce GTP hydrolysis due to a positive charged residue (K) substituted for an acidic residue (E) in the loop. A substitution of the acidic residue in FtsZ with G (FtsZ2) results in loss of GTPase activity.

Fig. 2

FtsZ filaments are tethered to the membrane by FtsA and ZipA. ZipA and FtsA bind to the highly conserved C-tail of FtsZ, which is connected to main body of FtsZ by a flexible linker. Both ZipA and FtsA are tethered to the membrane by a flexible linker that connects the membrane binding domains of these proteins to the main body of the protein.

Fig. 3

Antagonists of FtsZ assembly are positioned in the cell to spatially regulate tZ ring assembly. Nucleoid occlusion (NO) is mediated by SlmA in E. coli (Noc in B. subtilis) and prevents Z ring formation over the nucleoid. SlmA and Noc are localized by binding to sequences in the origin proximal region of the chromosome. The Min system prevents Z ring assembly near the poles. MinC is activated by being recruited to the membrane by MinD and oscillates between the poles of the cell under the control of MinD and MinE. In B. subtilis MinC/MinD are recruited to incipient septa by MinJ (not shown) and DivIVA. In Caulobacter crescentus MipZ forms a gradient on the nucleoid. The gradient emanates from its partner ParB, which is bound near the origin and anchored to the pole by interaction with PopZ. Following initiation of replication one origin segregates to the opposite pole where it dislodges FtsZ left over from the previous division. This FtsZ, along with newly synthesized FtsZ, assembles at the lowpoint of the bipolar MipZ gradient.

Fig. 4

Diagram of assembly of the Z ring and maturation to the divisome in E. coli. FtsZ polymers (FtsZ[n]) are tethered to the membrane by FtsA and ZipA, which leads to formation of the Z ring. However, FtsA is not immediately available to recruit downstream proteins (FtsA[i]). Although not essential, several FtsZ interacting proteins (ZapA–D) localize to the ring and promote the integrity of the Z ring. Antagonists of FtsZ assembly, MinC/D and SlmA, are positioned away from midcell so that it is permissive for Z ring formation. When enough monomeric FtsA (active [a]) is present at the Z ring the remaining Fts proteins and PBP1b are recruited. The arrival of FtsN signals the divisome is complete and activation of septal PG synthesis occurs (divisome [a]). The septal cross wall is split by AmiB, which is activated by EnvC (recruited earlier), and AmiC, which is activated by NlpD. Although EnvC is recruited early, the arrival of AmiC, AmiB and NlpD depend upon the start of septal PG synthesis induced by the arrival of FtsN. The Tol-Pal complex is needed for efficient invagination of the outer membrane.

Fig. 5

Structures of FtsA and MreB. Two molecules of FtsA are shown as arranged in a filament. The structure of MreB is similar to conventional actin. FtsA lacks domain 1B but has a new domain 1C (colored red in one FtsA) that interacts with other division proteins.