Splitsville: structural and functional insights into the dynamic bacterial z ring

KEY POINTS * All cells must divide to proliferate, and most bacteria divide by splitting themselves into two during cytokinesis. Many bacteria divide by splitting into approximately equal

halves in a process called binary fission. Cytokinesis in bacteria is achieved by the divisome, a dedicated protein machine that is located at the site of cell division. Recent advances in

ultrastructural imaging, biochemistry and genetics of _Escherichia coli_ and other model bacterial species have helped to refine models of divisome function and regulation. * FtsZ, the

bacterial homologue of tubulin, is the principal driver of bacterial cytokinesis. _In vitro_, FtsZ assembles into single protofilaments in the presence of GTP. _In vivo_, these

protofilaments loosely assemble to encircle the cell at the site of division — called the Z ring — and are positioned there by species-specific spatial positioning proteins. * As FtsZ is a

soluble protein, FtsZ protofilaments must be tethered to the inner surface of the cytoplasmic membrane by additional proteins, including FtsA and ZipA in _E. coli_. This complex of FtsZ and

membrane tethers is called the proto-ring and has highly dynamic behaviour. * Although they do not form microtubules, FtsZ protofilaments self-associate to form bundles, either through

interactions with other FtsZ subunits or with several FtsZ-binding proteins that enhance bundling, including ZipA and Zap proteins. These lateral interactions between FtsZ protofilaments may

be important for the ability of FtsZ to divide a cell. * FtsA, a bacterial homologue of actin, is a key connector between the Z ring and other proteins of the divisome, all of which span

the membrane and some of which bind to the peptidoglycan layer. Once the divisome is completely assembled, it coordinates the inward constriction of the Z ring and cytoplasmic membrane with

the synthesis of the cell division septum, which is composed of peptidoglycan. FtsA is a key player in this coordination, which probably involves feedback signalling between the

peptidoglycan-binding divisome proteins and the Z ring. Biochemical characterization of FtsA remains a major challenge. * In addition to signalling in the divisome during the process of

cytokinesis, the divisome is regulated by mechanical, metabolic and stress inputs. FtsZ is a major target for these regulators, but other divisome proteins are also targets. Understanding

how divisome proteins are inhibited or stimulated will be valuable in the future design of divisome-specific antimicrobial compounds. ABSTRACT Bacteria must divide to increase in number and

colonize their niche. Binary fission is the most widespread means of bacterial cell division, but even this relatively simple mechanism has many variations on a theme. In most bacteria, the

tubulin homologue FtsZ assembles into a ring structure, termed the Z ring, at the site of cytokinesis and recruits additional proteins to form a large protein machine — the divisome — that

spans the membrane. In this Review, we discuss current insights into the regulation of the assembly of the Z ring and how the divisome drives membrane invagination and septal cell wall

growth while flexibly responding to various cellular inputs. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS

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institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS INSIGHTS INTO THE ASSEMBLY AND REGULATION OF THE BACTERIAL DIVISOME Article 31

July 2023 SINGLE-MOLECULE IMAGING REVEALS THAT Z-RING CONDENSATION IS ESSENTIAL FOR CELL DIVISION IN _BACILLUS SUBTILIS_ Article 18 March 2021 FUNCTION AND REGULATION OF THE DIVISOME FOR

MITOCHONDRIAL FISSION Article 03 February 2021 CHANGE HISTORY * _ 25 APRIL 2016 _Nature Reviews Microbiology_ 14, 305–319 (2016). In the sixth paragraph of the section 'FtsA and the

dynamics of proto-ring assembly', the sentence “Finally, an FtsZ mutant with decreased self-bundling _in vitro_ (FtsZ-E93R) has reduced function in cell division50, 51.” should have

read “However, an FtsZ mutant with increased self-bundling _in vitro_ (FtsZ-E93R) has reduced function in cell division50,51.” The authors apologize to the readers for any misunderstanding

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ACKNOWLEDGEMENTS The authors gratefully acknowledge support from the US National Institute of General Medical Sciences (R01-GM61074 to W.M.) and the US National Institute of Research

Resources (S10RR029552) for the use of the 3D-SIM microscope. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Microbiology and Molecular Genetics, McGovern Medical School, 6431

Fannin Street, Houston, 77030, Texas, USA Daniel P. Haeusser & William Margolin * Biology Department, Canisius College, 2001 Main Street, Buffalo, 14208, New York, USA Daniel P. Haeusser

Authors * Daniel P. Haeusser View author publications You can also search for this author inPubMed Google Scholar * William Margolin View author publications You can also search for this

author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to William Margolin. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests.

POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 POWERPOINT SLIDE FOR FIG. 5 GLOSSARY * Cytokinesis The

splitting of the contents of a cell to make two cells. * Nucleoids The nucleus-like organized structures of bacterial chromosomes. * Mycelium A filamentous, branched network of multinucleate

cells growing on a surface. * Lipid II flippase A membrane protein that transfers lipid-linked peptidoglycan precursors from the inner leaflet of the cytoplasmic membrane to the outer

leaflet of the cytoplasmic membrane, so that they can be incorporated into the cell wall. * Sidewall The peptidoglycan layer in many rod-shaped bacteria that is active in elongating the cell

and comprises most of the straight wall of the cell with the exception of cell poles and the division septum. * Thermosensitive _ftsZ_ mutant A point mutation in the _ftsZ_ gene that

permits normal growth and division at 30 °C but stops division at 42 °C despite continued growth, resulting in filamentous, multinucleate cells (hence the term _fts_ for filamentous

temperature sensitive mutants). * Central metabolism Metabolic pathways, such as the tricarboxylic acid (TCA) cycle, that provide precursor metabolites for all other pathways that are

required for growth. * ClpXP A protein chaperone–protease machine that targets certain proteins for unfolding and degradation. * SOS response Induced by DNA damage, the SOS response is a

stress response that results in the expression of many genes that are important for the protection of chromosomal DNA. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE

THIS ARTICLE Haeusser, D., Margolin, W. Splitsville: structural and functional insights into the dynamic bacterial Z ring. _Nat Rev Microbiol_ 14, 305–319 (2016).

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