Close

Two FtsZ proteins orchestrate archaeal cell division through distinct functions in ring assembly and constriction

Yan Liao, Solenne Ithurbide, Jan Löwe, Iain G. Duggin

Preprint posted on 5 June 2020 https://www.biorxiv.org/content/10.1101/2020.06.04.133736v1

Article now published in Nature Microbiology at http://dx.doi.org/10.1038/s41564-021-00894-z

A second FtsZ isoform is recruited to constrict archaea that divide without a cell wall

Selected by Dey Lab

Gabriel Risa [1] and Gautam Dey [1]
[1] MRC lab for Molecular Cell Biology, UCL, London WC1E 6BT, UK

Context

What are FtsZs?

FtsZs are cytoskeletal proteins belonging to the tubulin superfamily found in bacteria, archaea, and some eukaryotic organelles with bacterial ancestry, e.g. plastids (Figure 1). The superfamily is characterised by its GTPase protein domain, which is critical for the proteins’ ability to dynamically assemble into filaments and drive cell shape changes.

What is the cell biological role of FtsZ in bacteria?

FtsZ plays a key role in the bacterial cell division machinery. It is an essential protein in almost all walled bacteria and among the first to assemble at the division site, where it forms part of the Z-ring machinery responsible for cell division (Du and Lutkenhaus, 2017). During cell division, FtsZ treadmilling directs peptidoglycan septal wall synthesis that drives constriction (Bisson-Filho et al., 2017).

Figure 1: Tubulin superfamily phylogenetic tree. The tree is based on alignment of tubulin superfamily proteins encoded in a set of 60 diverse archaeal genome sequences, with the bacterial and plant FtsZ sequences that were used to identify them. Statistical support for selected branches is given (bootstrap, %). The two archaeal FtsZ groups are defined by the presence of reference proteins from H. volcanii. Some non-canonical deeply branching FtsZ-like sequences present in Thaumarchaeota, Korarchaeota and others of unknown function, as well as the CetZ family (involved in cell shape), were also identified. Reproduced without modification from Figure 1 of Liao, Ithurbide et al. 2020 under a CC-BY-NC-ND 4.0 International License.

 

What role does FtsZs play in archaea?

FtsZs and CetZs (an archaea-specific tubulin superfamily protein) are found in several archaea (Figure 1). In contrast to bacteria, where normally only one FtsZ homologue is present, archaea often have two FtsZ homologues and numerous CetZ homologues. Intriguingly, whether an archaeon has one or two FtsZ homologues appears to coincide with whether the archaeon has a firm bacterial-like pseudomurein cell wall or a flexible S-layer, respectively.

 The archaeon Haloferax volcanii has a single flexible S-layer, two FtsZ homologues, and six CetZs. None of the CetZ homologues are individually required for division, albeit at least one contributes to cell shape (Hartman et al., 2010, Duggin et al., 2015). This work by Liao, Ithurbide et al. examines the cell division of H. volcanii in the context of FtsZ. Their findings offer new insights into how two FtsZ homologues take on different roles to drive cell division in soft archaea.

Key findings

Genetic perturbations of ftsZ1 and ftsZ2 lead to division defects in H. volcanii

Remarkably and unlike bacteria, H. volcanii cells were able to grow and divide in the absence of one or both ftsZ1 and ftsZ2 genes. Nevertheless, through a series of genetic perturbations, Liao, Ithurbide et al. showed that FtsZ1 is key to cell shape and both FtsZ1 and FtsZ2 are important for the cell division process (Figure 2). Cells expressing only ftsZ1 appeared enlarged and rod-shaped, and overexpressing ftsZ1 led WT and deletion strains to form longer rod-shaped cells. In contrast, cells expressing only ftsZ2 were enlarged but discoid, and overexpressing ftsZ2 led WT cells to become smaller. In the ΔftsZ1 deletion strain, overexpressing ftsZ2 led to a partial reversion to WT morphology. In summary, it seems cells become more elongated the more FtsZ1 there is relative to FtsZ2, and overexpression of FtsZ2 can at least partially rescue the loss of FtsZ1.

Figure 2: H. volcanii morphologies upon genetic perturbations of FtsZ. (Top 3 panels) Phase contrast micrographs of H. volcanii wild-type, FtsZ1 overproduction and FtsZ2 overproduction strains. (Bottom left 6 panels) Phase-contrast microscopy of the two ftsZ deletion strains containing ftsZ expression plasmids, with the indicated concentrations of Trp. (Bottom right 4 panels) Cross-complementation strains. Reproduced without modification from Figures 3 and 4 of Liao, Ithurbide et al. 2020 under a CC-BY-NC-ND 4.0 International License.

 

FtsZ1 and FtsZ2 collaborate during H. volcanii cell division

The authors expressed fluorescently labelled versions of ftsZ1 and ftsZ2 to observe their localisation and behaviour during cell divisions in WT and deletion strains (Figure 3). This was done at low levels of induction, as high levels of labelled proteins interfered with the division process (more a problem with FtsZ2-FP than FtsZ1-FP). FtsZ1 and FtsZ2 both co-localised at the division site and constricted together. In ΔftsZ2 cells, FtsZ1 appeared in ring-like structures, but these did not constrict. In ΔftsZ1 cells, FtsZ2 appeared in puncta and only rarely in rings. However, in some cases where FtsZ2 did appear in rings, it was also capable of constricting.

Figure 3: Fluorescence microscopy of H. volcanii strains. Expression at 0.2 mM Trp unless otherwise specified. (Top) co-localization of FtsZ1-mCh and FtsZ2-GFP fluorescence in cells. (Right) selected examples of dividing cells. (Bottom) Localization of each FtsZ in the absence of the other FtsZ. Reproduced without modification from Figures 5 and 6 of Liao, Ithurbide et al. 2020 under a CC-BY-NC-ND 4.0 International License.

 

The above observations and further in-depth analysis on the degree of localisation interdependence, led the authors to propose that FtsZ1 likely plays a more structural and stabilising role compared to FtsZ2 during cell division. Furthermore, they suggest that FtsZ1 is likely recruited prior to FtsZ2 at the division site and that FtsZ2 is the homologue largely responsible for constriction. 

 

Perspectives

Liao, Ithurbide et al. present here a working model for H. volcanii cell division. In doing so, the authors provide a suitable model organism for the study of how FtsZ mediates division in cells with a flexible S-layer, where cell wall synthesis is unlikely to drive constriction. FtsZ is one of the most conserved division proteins on the planet and therefore of great interest to the scientific community, and this work provides valuable new ground on which to build a greater understanding of its operative principles. 

 

Questions for the authors 

See questions and author response below!

 

References

  1. Bisson-Filho, A.W., Hsu, Y.P., Squyres, G.R., Kuru, E., Wu, F., Jukes, C., Sun, Y., Dekker, C., Holden, S., VanNieuwenhze, M.S., et al. (2017). Treadmilling by FtsZ filaments drives peptidoglycan synthesis and bacterial cell division. Science 355, 739-743.
  2.   Du, S., and Lutkenhaus, J. (2017). Assembly and activation of the Escherichia coli divisome. Mol Microbiol 105, 177-187.
  3.   Duggin, I.G., Aylett, C.H., Walsh, J.C., Michie, K.A., Wang, Q., Turnbull, L., Dawson, E.M., Harry, E.J., Whitchurch, C.B., Amos, L.A., et al. (2015). CetZ tubulin-like proteins control archaeal cell shape. Nature 519, 362-365.
  4.   Hartman, A.L., Norais, C., Badger, J.H., Delmas, S., Haldenby, S., Madupu, R., Robinson, J., Khouri, H., Ren, Q., Lowe, T.M., et al. (2010). The complete genome sequence of Haloferax volcanii DS2, a model archaeon. PLoS One 5, e9605.

 

 

Tags: archaea, cell division, ftsz

Posted on: 25 June 2020

doi: https://doi.org/10.1242/prelights.22237

Read preprint (No Ratings Yet)

The authors respond to questions raised in the post

Iain Duggin and co-authors shared

  1. What is known about the treadmilling and polymerisation rates and copolymerisation properties of FtsZ1 and FtsZ2 in H. volcanii

 

Ultra-structure and dynamics are of interest in future work through the development of further labels. Our movies show that the archaeal Z-rings are dynamic within the ring during the cell cycle, consistent with treadmilling, dynamic instability or potentially other types of polymer behaviour. 

 

  1. How might FtsZ1 and FtsZ2 constrict the cell and how relevant do you think treadmilling and S-layer synthesis is for the mechanism?

 

Our results suggest that FtsZ1 stabilizes the FtsZ2-based constriction apparatus. The flexible nature of the envelope suggests that a fundamentally different mechanism is required to maintain an inward constriction compared to walled bacteria that can continuously build the wall inwards. FtsZ2 appears to be required when there is no wall, suggesting it might have fundamentally a similar function in maintaining inward constriction. Several ratchet-like structural mechanisms can be imagined, and will be an important area of mechanobiology in comparison to the bacterial systems in future. 

 

  1. In the apparent absence of Min system dependent positioning of FtsZ, how might FtsZ1 and FtsZ2 be positioned?

 

It is likely that a min-like pattern-forming system (yet to be identified) helps position FtsZ at mid-cell in archaea (Walsh et al. 2019 Mol. Microbiol. 112: 785.)

 

  1. Do the FtsZ1 structures generally appear a specific distance from the cell poles in ΔftsZ2 cells?

 

Yes. In filamentous H. volcanii, rings frequently appear 3-4 micron from one or both poles. This suggests they are positioned under the influence of a cell shape/size-sensing system. More discoveries to be made!

 

  1. Could the authors comment on the presence and expected role of FtsZs in Asgard archaea?

 

Specific homologs of both FtsZ1 and FtsZ2 are present in some of the individual Asgard archaea that we examined. We would expect they are involved in division, but this requires further study; detection of the subcellular localization of these and other candidate cell division proteins in cultivated Asgard archaea would be an interesting first step. Some species only contain one FtsZ, but the genomes are incomplete.

Have your say

Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Sign up to customise the site to your preferences and to receive alerts

Register here

preLists in the biochemistry category:

20th “Genetics Workshops in Hungary”, Szeged (25th, September)

In this annual conference, Hungarian geneticists, biochemists and biotechnologists presented their works. Link: http://group.szbk.u-szeged.hu/minikonf/archive/prg2021.pdf

 



List by Nándor Lipták

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

MitoList

This list of preprints is focused on work expanding our knowledge on mitochondria in any organism, tissue or cell type, from the normal biology to the pathology.

 



List by Sandra Franco Iborra

Also in the cell biology category:

Fibroblasts

The advances in fibroblast biology preList explores the recent discoveries and preprints of the fibroblast world. Get ready to immerse yourself with this list created for fibroblasts aficionados and lovers, and beyond. Here, my goal is to include preprints of fibroblast biology, heterogeneity, fate, extracellular matrix, behavior, topography, single-cell atlases, spatial transcriptomics, and their matrix!

 



List by Osvaldo Contreras

EMBL Synthetic Morphogenesis: From Gene Circuits to Tissue Architecture (2021)

A list of preprints mentioned at the #EESmorphoG virtual meeting in 2021.

 



List by Alex Eve

FENS 2020

A collection of preprints presented during the virtual meeting of the Federation of European Neuroscience Societies (FENS) in 2020

 



List by Ana Dorrego-Rivas

Planar Cell Polarity – PCP

This preList contains preprints about the latest findings on Planar Cell Polarity (PCP) in various model organisms at the molecular, cellular and tissue levels.

 



List by Ana Dorrego-Rivas

BioMalPar XVI: Biology and Pathology of the Malaria Parasite

[under construction] Preprints presented at the (fully virtual) EMBL BioMalPar XVI, 17-18 May 2020 #emblmalaria

 



List by Dey Lab, Samantha Seah

1

Cell Polarity

Recent research from the field of cell polarity is summarized in this list of preprints. It comprises of studies focusing on various forms of cell polarity ranging from epithelial polarity, planar cell polarity to front-to-rear polarity.

 



List by Yamini Ravichandran

TAGC 2020

Preprints recently presented at the virtual Allied Genetics Conference, April 22-26, 2020. #TAGC20

 



List by Maiko Kitaoka et al.

3D Gastruloids

A curated list of preprints related to Gastruloids (in vitro models of early development obtained by 3D aggregation of embryonic cells). Updated until July 2021.

 



List by Paul Gerald L. Sanchez and Stefano Vianello

ECFG15 – Fungal biology

Preprints presented at 15th European Conference on Fungal Genetics 17-20 February 2020 Rome

 



List by Hiral Shah

ASCB EMBO Annual Meeting 2019

A collection of preprints presented at the 2019 ASCB EMBO Meeting in Washington, DC (December 7-11)

 



List by Madhuja Samaddar et al.

EMBL Seeing is Believing – Imaging the Molecular Processes of Life

Preprints discussed at the 2019 edition of Seeing is Believing, at EMBL Heidelberg from the 9th-12th October 2019

 



List by Dey Lab

Autophagy

Preprints on autophagy and lysosomal degradation and its role in neurodegeneration and disease. Includes molecular mechanisms, upstream signalling and regulation as well as studies on pharmaceutical interventions to upregulate the process.

 



List by Sandra Malmgren Hill

Lung Disease and Regeneration

This preprint list compiles highlights from the field of lung biology.

 



List by Rob Hynds

Cellular metabolism

A curated list of preprints related to cellular metabolism at Biorxiv by Pablo Ranea Robles from the Prelights community. Special interest on lipid metabolism, peroxisomes and mitochondria.

 



List by Pablo Ranea Robles

BSCB/BSDB Annual Meeting 2019

Preprints presented at the BSCB/BSDB Annual Meeting 2019

 



List by Dey Lab

Biophysical Society Annual Meeting 2019

Few of the preprints that were discussed in the recent BPS annual meeting at Baltimore, USA

 



List by Joseph Jose Thottacherry

ASCB/EMBO Annual Meeting 2018

This list relates to preprints that were discussed at the recent ASCB conference.

 



List by Dey Lab, Amanda Haage

Also in the evolutionary biology category:

Close