GTPase activity-coupled treadmilling of the bacterial tubulin FtsZ organizes septal cell-wall synthesis

Abstract

The bacterial tubulin FtsZ is the central component of the division machinery, coordinating an ensemble of proteins involved in septal cell-wall synthesis to ensure successful constriction. How cells achieve this coordination is unknown. We used a combination of imaging, genetic and biochemical approaches to demonstrate that in Escherichia coli cells FtsZ exhibits dynamic treadmilling predominantly determined by its GTPase activity, and that the treadmilling dynamics directs processive movement of the septal cell-wall synthesis machinery. In FtsZ mutants with severely reduced treadmilling, the spatial distribution of septal synthesis and the molecular composition and ultrastructure of the septal cell wall are substantially altered. Thus, the treadmilling of FtsZ provides a novel and robust mechanism for achieving uniform septal cell-wall synthesis to enable correct new pole morphology.One-sentence summaryThe bacterial tubulin FtsZ uses GTP hydrolysis to power treadmilling, driving processive synthesis of the septal cell wall.

Species‐ and C‐terminal linker‐dependent variations in the dynamic behavior of FtsZ on membranes in vitro

“…Which, if any, of the superstructures formed by Ec FtsZ or Cc FtsZ on SLBs in vitro are relevant in the physiological context of Z‐ring assembly? Individual clusters of FtsZ protofilaments in Z‐rings in vivo are asymmetric and shorter than 200 nm in length as observed by electron cryotomography (Li et al, ) or super‐resolution light microscopy (Fu et al, ; Holden et al, ; Yang et al, ), most similar to the precursors of Cc FtsZ or Ec FtsZ superstructures we observe here. In contrast, the emergent bundles of Ec FtsZ at steady state extend longer than 2 µm, dimensions not reported in cells for E. coli FtsZ.…”

Assembly and activation of the Escherichia coli divisome

“…The septal PG synthases FtsW and FtsI along with the other divisome proteins follow the movement of FtsZ polymers to distribute PG synthesis around the septum likely because they form a complex with FtsA which chases the movement of FtsZ polymers by binding to the CCTPs of FtsZ polymers. Reducing the GTPase activity of FtsZ slows down the movement of FtsZ polymers at the Z ring and leads to uneven incorporation of septal PG, resulting in the formation of distorted septa (Yang et al ., ). One can imagine FtsZ polymers as trains running in shrinking circles and the PG synthases as workers that distribute the building blocks to form the septum.…”

Bacterial Cell Size: Multifactorial and Multifaceted

“…The most likely candidate for a cell division dependent sizer appears to be FtsZ, a highly conserved tubulin-like GTPase that forms a discontinuous ring at the nascent division site [reviewed here (46)]. FtsZ is the first of the conserved cell division proteins to localize to the division site where recent work suggests it forms a treadmilling platform for assembly and function of the cell division (35, 108). …”

“…While experimental evidence supporting the former is limited (38, 1, 23), there is significant data supporting the potential for an enhanced rate of cytokinesis contributing to the reduced size of ftsA* and ftsL* mutants. Most importantly, in E. coli conditional mutations in the FtsI transpeptidase, a late protein dependent on both FtsA and FtsL for localization, significantly reduce the rate of septal wall synthesis and increase E. coli cell length, suggesting that septal wall synthesis is rate limiting for division (21, 108). Gain-of-function mutations in periplasmic domains of the FtsI and its putative cognate transglycosylase, FtsW, have also been show to reduce the size of C. crescentus cells (70).…”