Close

Closed mitosis requires local disassembly of the nuclear envelope

Gautam Dey, Siân Culley, Scott Curran, Ricardo Henriques, Wanda Kukulski, Buzz Baum

Posted on: 3 February 2020 , updated on: 18 June 2021

Preprint posted on 23 September 2019

Article now published in Nature at http://dx.doi.org/10.1038/s41586-020-2648-3

What is the mechanism behind closed mitosis in S.pombe? Dey et al. show how a protein named ‘Les1’ ensures the local disassembly of the nuclear envelope on the bridge that connects the two daughter nuclei, thus preventing leakage of nuclear material

Selected by Leeba Ann Chacko

Video depicting the sequence of events during nuclear envelope breakdown in S.pombe cells with and without Les1

Background: 

Cell division is a fundamental process for life wherein a cell divides into two identical daughter cells. The purpose of cell division is to enable the growth, propagation, and replacement of damaged cells. During cell division, cells duplicate their nuclear compartment containing DNA. Mitosis is the process in which these nuclear compartments separate into two independent daughter nuclei.

In most mammalian cells which have open mitosis, one of the key steps in mitosis is the breakdown of the nuclear envelope. However, this is not a universal feature of mitosis among all cells and organisms. Some organisms such as unicellular yeasts are known to undergo ‘closed mitosis’, wherein the nuclear envelope remains intact throughout the cell cycle. Interestingly, as the nucleus divides, it undergoes major shape changes wherein prior to division, it transforms from a spherical to an elongated shape. Correspondingly, after division, the nucleus reverts to its spherical shape.

In fission yeast, at the onset of mitosis, the nucleus transforms from a spherical to a dumbbell shape and then constricts to form a thin nuclear bridge between the two daughter nuclei that ultimately split. Interestingly, during this entire process, the nuclear contents remain intact. Dey et al. show that a novel, uncharacterized protein named ‘Les1’ plays a crucial role in keeping the nuclear compartment boundary intact during cell division.

Key findings: 

1) An uncharacterized protein (locus tag SPAC23C4.05c) shows a unique localization pattern, wherein it forms stalks in the inner surface of the thin nuclear bridge between the two daughter nuclei, during the early stages of the bridge formation. As the bridge elongates, Les1 visibly becomes depleted from the mid-zone of the bridge. The authors named the protein ‘Les1’.

2) Since Les1 is localized to the stalks at the midzone, the authors looked at the intersection between the midzone and the stalk of dividing nuclei with the help of electron tomograms. Strikingly, these images show that while the spindle is enveloped by Les1 at the stalks, the midzone region of the spindle is directly projected into the cytoplasm with nothing but a few strands of the endoplasmic reticulum.

3) Two components of the nuclear pore complex (NPC), namely Cut11 and Nup60, show mutually exclusive localization with respect to Les1. Like what is observed in open mitosis, the NPCs dissociate from the nuclear envelope, thereby leading to its breakdown. The components of the NPC dissociate in a sequential manner with membrane Nups being lost last as the nuclear localization signal disappears from the midzone. Thus, the steps of local NEB at the midzone of the bridge are similar to NEB in open mitosis.

4) Finally, the authors found that when Les1 is removed, the NPCs are localized across the bridge and as a consequence, the bridge is divided in arbitrary locations away from the mid-zone. These random tears in turn lead to leakages in nuclear material from at least one of the two daughter nuclei. Thus, Les1 is required to prevent such leakage from happening.   

What I liked about this preprint: 

I came across this preprint when it was posted on Twitter. It was a very interactive post that got me wondering why I never thought about how closed mitosis occurs without affecting the nuclear membrane. I now know that the protein ‘Les1’ restricts NPCs to the mid-zone and thereby prevents leakage from daughter nuclei.

The post also shows how making science easily accessible and interactive can get people to engage in scientific questions that they might never have thought about in the first place.

References:

1. Dey, G., Culley, S., Curran, S., Henriques, R., Kukulski, W., & Baum, B. (2019). Closed mitosis requires local disassembly of the nuclear envelope. bioRxiv, 779769.

2. Boettcher, B., & Barral, Y. (n.d.). The cell biology of open and closed mitosis. Nucleus (Austin, Tex.), 4(3), 160–165.

Tags: les1, mitosis, nucleus, s.pombe

doi: https://doi.org/10.1242/prelights.16627

Read preprint (No Ratings Yet)

Author's response

Gautam Dey shared

Our reviewers and editor at Nature were interested in the core discovery of local NEB presented in the preprint, but suggested that the paper needed more mechanistic evidence to a) clarify the role of Les1 in this process, and b) elucidate the mechanism of NPC disassembly. In addressing their comments (details below), we believe we produced an improved, stronger manuscript, and we thank them for their feedback!

Key preprint-paper changes:

1) We include a more detailed characterisation of the Les1 deletion phenotype (including CLEM of the mutant strain and partial rescue through altering membrane availability, Figure 4);

2) We show that Imp1 is required for NPC disassembly in the bridge, local NEB and consequently for spindle disassembly (Figure 3 and Extended Data);

3) We show that nuclear basket proteins are excluded from bridge NPCs (Figure 3 and Extended Data);

4) We show that ESCRTIII (Cmp7/Lem2) is recruited to stalk tips, and required to maintain daughter nucleus integrity independent of Les1; both proteins are synthetically lethal with Les1 (Figure 4 and Extended Data).

preLight questions:

1) Do you have any clues on what is preventing the localisation of Les1 throughout the mid-zone region during the later stages of the bridge assembly? Is it possible to visualise Les1 signal in the absence of NPCs?

We don’t yet understand the molecular mechanism leads to Les1 depletion – except that areas of NPC accumulation always correspond to areas of (relative) Les1 depletion, even under mutant conditions that displace NPCs from the bridge midzone. We are looking for ways to perturb NPC localisation or clustering independent of Les1 to try and address the causal relationships behind these mutually exclusive localisation patterns.

2) You have shown that in the absence of Les1, nuclear leakages occur (Figure 4). Do you have any clues on why these leakages are mostly isolated to one of the daughter nuclei?

Great question! We don’t know why this is the case, but speculate that, as the initial loss of integrity can occur at any point along the bridge, the leakage is most likely to affect the daughter nucleus closest to the break point – following which it is rapidly repaired by ESCRTIII proteins.

3) Will you be looking for proteins that are analogous to Les1 in other organisms that undergo closed mitosis? Do you think the mechanism would be similar?

Les1 and its paralog Ish1 appear restricted to Schizosaccharomyces and a few related fungal lineages – Saccharomyces cerevisiae has a single homolog, a protein of unknown function named Msc1 (Extended Data Figure 1). However, the Ish1 motif shared by all these proteins is related to the LEM/SAP/HeH domain superfamily present in many nuclear envelope proteins across eukaryotes. We expect that key members of this superfamily would play analogous roles to Les1 in other systems.

Have your say

Your email address will not be published. Required fields are marked *

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

Also in the bioinformatics category:

Expressive modeling and fast simulation for dynamic compartments

Till Köster, Philipp Henning, Tom Warnke, et al.

Selected by 18 April 2024

Benjamin Dominik Maier

Systems Biology

Transcriptional profiling of human brain cortex identifies novel lncRNA-mediated networks dysregulated in amyotrophic lateral sclerosis

Alessandro Palma, Monica Ballarino

Selected by 16 April 2024

Julio Molina Pineda

Genomics

Spatial transcriptomics elucidates medulla niche supporting germinal center response in myasthenia gravis thymoma

Yoshiaki Yasumizu, Makoto Kinoshita, Martin Jinye Zhang, et al.

Selected by 27 March 2024

Jessica Chevallier

Immunology

Also in the cell biology category:

Control of Inflammatory Response by Tissue Microenvironment

Zhongyang Wu, Scott D. Pope, Nasiha S. Ahmed, et al.

Selected by 13 June 2024

Roberto Amadio

Immunology

Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping

Tobias Holm Bønnelykke, Marie-Amandine Chabry, Emeline Perthame, et al.

Selected by 06 June 2024

Bhaval Parmar

Developmental Biology

LINC complex alterations are a hallmark of sporadic and familial ALS/FTD

Riccardo Sirtori, Michelle Gregoire, Emily Potts, et al.

Selected by 03 June 2024

Megane Rayer et al.

Cell Biology

Also in the genetics category:

Lipid-Based Transfection of Zebrafish Embryos: A Robust Protocol for Nucleic Acid Delivery

Aslihan Terzi, Tiger Liao, Adrian Jacobo

Selected by 09 May 2024

Roberto Rodríguez-Morales

Genetics

Temporal constraints on enhancer usage shape the regulation of limb gene transcription

Raquel Rouco, Antonella Rauseo, Guillaume Sapin, et al.

Selected by 17 April 2024

María Mariner-Faulí

Developmental Biology

A long non-coding RNA at the cortex locus controls adaptive colouration in butterflies

Luca Livraghi, Joseph J. Hanly, Elizabeth Evans, et al.

AND

The ivory lncRNA regulates seasonal color patterns in buckeye butterflies

Richard A. Fandino, Noah K. Brady, Martik Chatterjee, et al.

AND

A micro-RNA drives a 100-million-year adaptive evolution of melanic patterns in butterflies and moths

Shen Tian, Tirtha Das Banerjee, Jocelyn Liang Qi Wee, et al.

Selected by 05 April 2024

Isabella Cisneros

Developmental Biology

Also in the microbiology category:

Characterization of natural product inhibitors of quorum sensing in Pseudomonas aeruginosa reveals competitive inhibition of RhlR by ortho-vanillin

Kathryn E. Woods, Sana Akhter, Blanca Rodriguez, et al.

Selected by 22 May 2024

UofA IMB565 et al.

Microbiology

Feedback loop regulation between viperin and viral hemorrhagic septicemia virus through competing protein degradation pathways

Xiaobing Lu, Meisheng Yi, Zhe Hu, et al.

Selected by 21 May 2024

UofA IMB565 et al.

Immunology

Lytic bacteriophages interact with respiratory epithelial cells and induce the secretion of antiviral and proinflammatory cytokines

Paula F. Zamora, Thomas G. Reidy, Catherine R. Armbruster, et al.

Selected by 20 May 2024

UofA IMB565 et al.

Microbiology

preLists in the bioinformatics category:

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

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

Single Cell Biology 2020

A list of preprints mentioned at the Wellcome Genome Campus Single Cell Biology 2020 meeting.

 



List by Alex Eve

Antimicrobials: Discovery, clinical use, and development of resistance

Preprints that describe the discovery of new antimicrobials and any improvements made regarding their clinical use. Includes preprints that detail the factors affecting antimicrobial selection and the development of antimicrobial resistance.

 



List by Zhang-He Goh

Also in the cell biology category:

BSCB-Biochemical Society 2024 Cell Migration meeting

This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.

 



List by Reinier Prosee

‘In preprints’ from Development 2022-2023

A list of the preprints featured in Development's 'In preprints' articles between 2022-2023

 



List by Alex Eve, Katherine Brown

preLights peer support – preprints of interest

This is a preprint repository to organise the preprints and preLights covered through the 'preLights peer support' initiative.

 



List by preLights peer support

The Society for Developmental Biology 82nd Annual Meeting

This preList is made up of the preprints discussed during the Society for Developmental Biology 82nd Annual Meeting that took place in Chicago in July 2023.

 



List by Joyce Yu, Katherine Brown

CSHL 87th Symposium: Stem Cells

Preprints mentioned by speakers at the #CSHLsymp23

 



List by Alex Eve

Journal of Cell Science meeting ‘Imaging Cell Dynamics’

This preList highlights the preprints discussed at the JCS meeting 'Imaging Cell Dynamics'. The meeting was held from 14 - 17 May 2023 in Lisbon, Portugal and was organised by Erika Holzbaur, Jennifer Lippincott-Schwartz, Rob Parton and Michael Way.

 



List by Helen Zenner

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

CellBio 2022 – An ASCB/EMBO Meeting

This preLists features preprints that were discussed and presented during the CellBio 2022 meeting in Washington, DC in December 2022.

 



List by Nadja Hümpfer et al.

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

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

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 genetics category:

BSDB/GenSoc Spring Meeting 2024

A list of preprints highlighted at the British Society for Developmental Biology and Genetics Society joint Spring meeting 2024 at Warwick, UK.

 



List by Joyce Yu, Katherine Brown

BSCB-Biochemical Society 2024 Cell Migration meeting

This preList features preprints that were discussed and presented during the BSCB-Biochemical Society 2024 Cell Migration meeting in Birmingham, UK in April 2024. Kindly put together by Sara Morais da Silva, Reviews Editor at Journal of Cell Science.

 



List by Reinier Prosee

9th International Symposium on the Biology of Vertebrate Sex Determination

This preList contains preprints discussed during the 9th International Symposium on the Biology of Vertebrate Sex Determination. This conference was held in Kona, Hawaii from April 17th to 21st 2023.

 



List by Martin Estermann

Alumni picks – preLights 5th Birthday

This preList contains preprints that were picked and highlighted by preLights Alumni - an initiative that was set up to mark preLights 5th birthday. More entries will follow throughout February and March 2023.

 



List by Sergio Menchero et al.

Semmelweis Symposium 2022: 40th anniversary of international medical education at Semmelweis University

This preList contains preprints discussed during the 'Semmelweis Symposium 2022' (7-9 November), organised around the 40th anniversary of international medical education at Semmelweis University covering a wide range of topics.

 



List by Nándor Lipták

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

2nd Conference of the Visegrád Group Society for Developmental Biology

Preprints from the 2nd Conference of the Visegrád Group Society for Developmental Biology (2-5 September, 2021, Szeged, Hungary)

 



List by Nándor Lipták

EMBL Conference: From functional genomics to systems biology

Preprints presented at the virtual EMBL conference "from functional genomics and systems biology", 16-19 November 2020

 



List by Jesus Victorino

TAGC 2020

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

 



List by Maiko Kitaoka et al.

ECFG15 – Fungal biology

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

 



List by Hiral Shah

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

Zebrafish immunology

A compilation of cutting-edge research that uses the zebrafish as a model system to elucidate novel immunological mechanisms in health and disease.

 



List by Shikha Nayar
Close