FtsZ Ring Stability: of Bundles, Tubules, Crosslinks, and Curves

Abstract

The first step in bacterial cytokinesis is the assembly of a stable but dynamic cytokinetic ring made up of the essential tubulin homolog FtsZ at the future site of division. Although FtsZ and its role in cytokinesis have been studied extensively, the precise architecture of the in vivo medial FtsZ ring (Z ring) is not well understood. Recent advances in superresolution imaging suggest that the Z ring comprises short, discontinuous, and loosely bundled FtsZ polymers, some of which are tethered to the membrane. A diverse array of regulatory proteins modulate the assembly, stability, and disassembly of the Z ring via direct interactions with FtsZ. Negative regulators of FtsZ play a critical role in ensuring the accurate positioning of FtsZ at the future site of division and in maintaining Z ring dynamics by controlling FtsZ polymer assembly/disassembly processes. Positive regulators of FtsZ are essential for tethering FtsZ polymers to the membrane and promoting the formation of stabilizing lateral interactions, permitting assembly of a mature Z ring. The past decade has seen the identification of several factors that promote FtsZ assembly, presumably through a variety of distinct molecular mechanisms. While a few of these proteins are broadly conserved, many positive regulators of FtsZ assembly are limited to small groups of closely related organisms, suggesting that FtsZ assembly is differentially modulated across bacterial species. In this review, we focus on the roles of positive regulators in Z ring assembly and in maintaining the integrity of the cytokinetic ring during the early stages of division. Bacterial cytokinesis is mediated by a macromolecular protein machine that is accurately positioned in space and time during the cell cycle. The earliest defined event during cytokinesis is the assembly of a polymeric FtsZ structure at the site of future division known as the FtsZ ring, or Z ring (1). The Z ring serves as a scaffold for the recruitment of other division proteins (2-5). FtsZ, a tubulin homolog, forms homopolymeric linear protofilaments upon binding GTP, and these filaments subsequently disassemble upon hydrolysis of the bound nucleotide (6-9). Approximately 30% of cellular FtsZ is present in the ring, and fluorescence recovery after photobleaching (FRAP) studies reveal that there is dynamic exchange between FtsZ molecules in the ring polymers and FtsZ monomers or short oligomers in the cytoplasm (10, 11).In Escherichia coli and Bacillus subtilis, cytokinesis can be separated chronologically into the following three steps: (i) assembly and stabilization of the Z ring at the future division site and, following a lag, (ii) recruitment of downstream division proteins, many of which are essential to form a constriction-competent division complex, and lastly, (iii) constriction of the Z ring coordinated with synthesis and splitting of septal peptidoglycan, leading to invagination of the cell membrane and division into two daughter cells (Fig. 1A) (2, 12, 13). The force required for constriction is likely...

FtsEX acts on FtsA to regulate divisome assembly and activity

“…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).…”

“…The Z ring consists of FtsZ polymers tethered to the membrane by the membrane anchors FtsA and ZipA (4)(5)(6). A number of nonessential proteins, called Zaps (FtsZ-associated proteins, ZapA, ZapB, ZapC, and ZapD), coassemble with FtsZ to promote the integrity of the Z ring (7). FtsEX, an ATP-binding cassette transporter-like complex, and its interaction partner EnvC are also recruited to the Z ring at this step (8,9).…”

ClpXP and ClpAP control the Escherichia coli division protein ZapC by proteolysis

“…Imbalances in the levels of Z-ring regulatory proteins lead to division defects and altered cell lengths (Huang et al, 2013;Ortiz et al, 2016). ZapC stabilizes FtsZ polymers but ClpXP degrades FtsZ and, as we show here, both ClpXP and ClpAP degrade ZapC.…”

“…As FtsZ levels are essentially constant throughout the cell cycle, spatiotemporal control of division is exercised largely through the assembly/ disassembly of the Z-ring (Rueda et al, 2003;Weart & Levin, 2003). A number of proteins that interact with FtsZ contribute to its function by modulating the dynamics of FtsZassembly (Adams & Errington, 2009;Huang et al, 2013;Lutkenhaus et al, 2012;Ortiz et al, 2016). However, the precise molecular nature of the protein-protein interactions between FtsZ and FtsZ-regulators that yield a stable but dynamic Z-ring is not completely understood as yet.…”

Divided we stand: splitting synthetic cells for their proliferation

“…All these observations stress the importance of lateral interactions between the FtsZ protofilaments for the Z-ring organization. In vivo, these lateral interactions are mediated by multiple positive regulators (Huang et al 2013). Furthermore, in vitro the protofilaments are typically only about 100 nm long, while in vivo the Z-ring is a highly dynamic structure that constantly exchanges material with the cytoplasmic pool (Anderson et al 2004).…”