Dynamic Kinetochore Size Regulation Promotes Microtubule Capture And Chromosome Biorientation In Mitosis
Posted on: 26 March 2018
Preprint posted on 12 March 2018
Article now published in Nature Cell Biology at http://dx.doi.org/10.1038/s41556-018-0130-3
Self-assembly of the RZZ complex into filaments drives kinetochore expansion in the absence of microtubule attachment
Posted on:
Preprint posted on 15 March 2018
Article now published in Current Biology at http://dx.doi.org/10.1016/j.cub.2018.08.056
Catch me if you can: two preprints reveal the molecular interactions that allow outer kinetochores to expand and shrink dynamically in order to properly capture their microtubule targets in mitosis.
Selected by Dey Lab
Categories: biochemistry, cell biology, evolutionary biology
Context
The outer surfaces of kinetochores expand in early mitosis to form crescent-shaped structures thought to play an important role in forming proper chromosome-spindle attachments1. The crescent was named the “fibrous corona” for its distinctive appearance in early electron micrographs2. E.D. Salmon and colleagues demonstrated microtubule-dependent expansion and compaction in pioneering work3, but the fibrous corona’s complete molecular composition and proof of its predicted functional role have both proven somewhat elusive. Existing data on recruitment kinetics of various kinetochore components, along with structural predictions, hinted at starring roles for the ROD-ZW10-Zwilch (RZZ) complex and the dynein adaptor Spindly4.
Key findings
Sacristan et al., working in cell lines, first show that Spindly recruits dynein via three independent motifs to compact coronas. In vitro, purified RZZ complexes polymerise into filaments only in the presence of Spindly. In cells, Spindly uses its farnesyl (lipid) group to promote initial hydrophobic interactions with RZZ until phosphorylated and activated by the kinase Mps1. These conclusions are backed up by an impressive array of structural data. Expanded coronas that are incapable of shedding – as it is the case in Spindly mutants – form overly-stable “merotelic” attachments, in which chromosomes remain attached to microtubules from both poles.
Pereira, Reis et al. investigate the same RZZ-Spindly system in human cells, in vitro, and in C. elegans embryos. Chemically induced mitotic arrest, followed by forced mitotic exit, actually detaches the coronas from the centromeres, enabling the authors to assess their molecular composition – they find RZZ components, Spindly, CENP-E and the checkpoint proteins Mad1/2. Over-expression of only Rod produces expanded coronas, even when RZZ recruitment is impaired at an upstream step. Following up on this, the authors show that GFP-tagged Rod forms filaments in C. elegans embryos when it reaches a threshold concentration, but in a Spindly-independent fashion- an apparent discrepancy between humans and worms. Finally, the authors define a minimal RZZ complex capable of oligomerization in vitro.
Why I chose these papers
It’s not every day that a field makes large strides in demystifying a cellular structure of likely fundamental importance. In addition, the intrinsic simplicity of the Spindly-RZZ system that emerges from these papers – despite the complexity of the spatial feedback loop it must execute – greatly appeals to me.
RZZ appears to share an evolutionary history with ancient nuclear pore and vesicle coat proteins5. The unusual combination of beta-propeller and alpha-solenoid domains that these proteins share played a fundamental role in the evolution of eukaryotes6 – raising the exciting possibility that RZZ will help us learn more about the evolution of the kinetochore7 and its role in early eukaryotic cell division.
What next?
New imaging and analytical tools have made it possible to track kinetochore dynamics in real-time with impressive resolution8. Applying these tools to RZZ and Spindly mutants will likely produce additional insights into the role of the fibrous corona in microtubule capture.
Of related recent interest in kinetochore biology
Not all kinetochores are the same! Check out these two preprints from the McClelland9 and Maiato10 labs on the differences in (mis)segregation behaviour between different chromosomes in a single cell.
References:
- Maiato, H., DeLuca, J., Salmon, E. D. & Earnshaw, W. C. The dynamic kinetochore-microtubule interface. J. Cell Sci. 117, 5461–77 (2004).
- McEwen, B. F., Arena, J. T., Frank, J. & Rieder, C. L. Structure of the colcemid-treated PtK1 kinetochore outer plate as determined by high voltage electron microscopic tomography. J. Cell Biol. 120, 301–12 (1993).
- Hoffman, D. B., Pearson, C. G., Yen, T. J., Howell, B. J. & Salmon, E. D. Microtubule-dependent changes in assembly of microtubule motor proteins and mitotic spindle checkpoint proteins at PtK1 kinetochores. Mol. Biol. Cell 12, 1995–2009 (2001).
- Mosalaganti, S. et al. Structure of the RZZ complex and molecular basis of its interaction with Spindly. J. Cell Biol. 216, 961–981 (2017).
- Civril, F. et al. Structural analysis of the RZZ complex reveals common ancestry with multisubunit vesicle tethering machinery. Structure 18, 616–26 (2010).
- Baum, D. A. A comparison of autogenous theories for the origin of eukaryotic cells. Am. J. Bot. 102, 1954–65 (2015).
- van Hooff, J. J., Tromer, E., van Wijk, L. M., Snel, B. & Kops, G. J. Evolutionary dynamics of the kinetochore network in eukaryotes as revealed by comparative genomics. EMBO Rep. 18, 1559–1571 (2017).
- Burroughs, N. J., Harry, E. F. & McAinsh, A. D. Super-resolution kinetochore tracking reveals the mechanisms of human sister kinetochore directional switching. Elife 4, (2015).
- Worrall, J. T. et al. Non-Random Mis-Segregation of Human Chromosomes. bioRxiv 278697 (2018). doi:10.1101/278697
- Drpic, D., Almeida, A., Aguiar, P. & Maiato, H. Chromosome (mis)segregation is biased by kinetochore size. bioRxiv 278572 (2018). doi:10.1101/278572
(No Ratings Yet)Sign up to customise the site to your preferences and to receive alerts
Register hereAlso in the biochemistry category:
Triglyceride metabolism controls inflammation and APOE4-associated disease states in microglia
Gustavo Stelzer, Marcus Oliveira
Impaired 26S proteasome causes learning and memory deficiency and induces neuroinflammation mediated by NF-κB in mice
Gustavo Stelzer, Marcus Oliveira
Notch3 is a genetic modifier of NODAL signalling for patterning asymmetry during mouse heart looping
Bhaval Parmar
Also in the cell biology category:
Restoring mechanophenotype reverts malignant properties of ECM-enriched vocal fold cancer
Teodora Piskova
Germplasm stability in zebrafish requires maternal Tdrd6a and Tdrd6c
Justin Gutkowski
Leukocytes use endothelial membrane tunnels to extravasate the vasculature
Felipe Del Valle Batalla
Also in the evolutionary biology category:
Geometric analysis of airway trees shows that lung anatomy evolved to enable explosive ventilation and prevent barotrauma in cetaceans
Sarah Young-Veenstra
Enhancer-driven cell type comparison reveals similarities between the mammalian and bird pallium
Rodrigo Senovilla-Ganzo
Modular control of time and space during vertebrate axis segmentation
AND
Natural genetic variation quantitatively regulates heart rate and dimension
Girish Kale, Jennifer Ann Black
preLists in the biochemistry 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 |
Peer Review in Biomedical Sciences
Communication of scientific knowledge has changed dramatically in recent decades and the public perception of scientific discoveries depends on the peer review process of articles published in scientific journals. Preprints are key vehicles for the dissemination of scientific discoveries, but they are still not properly recognized by the scientific community since peer review is very limited. On the other hand, peer review is very heterogeneous and a fundamental aspect to improve it is to train young scientists on how to think critically and how to evaluate scientific knowledge in a professional way. Thus, this course aims to: i) train students on how to perform peer review of scientific manuscripts in a professional manner; ii) develop students' critical thinking; iii) contribute to the appreciation of preprints as important vehicles for the dissemination of scientific knowledge without restrictions; iv) contribute to the development of students' curricula, as their opinions will be published and indexed on the preLights platform. The evaluations will be based on qualitative analyses of the oral presentations of preprints in the field of biomedical sciences deposited in the bioRxiv server, of the critical reports written by the students, as well as of the participation of the students during the preprints discussions.
| List by | Marcus Oliveira 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. |
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:
November in preprints – the CellBio edition
This is the first community-driven preList! A group of preLighters, with expertise in different areas of cell biology, have worked together to create this preprint reading lists for researchers with an interest in cell biology. Categories include: 1) cancer cell biology 2) cell cycle and division 3) cell migration and cytoskeleton 4) cell organelles and organisation 5) cell signalling and mechanosensing 6) genetics/gene expression
| List by | Felipe Del Valle Batalla et al. |
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 |
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:
‘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 |
EMBO | EMBL Symposium: The organism and its environment
This preList contains preprints discussed during the 'EMBO | EMBL Symposium: The organism and its environment', organised at EMBL Heidelberg, Germany (May 2023).
| List by | Girish Kale |
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 |
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 |
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 |
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 |
COVID-19 / SARS-CoV-2 preprints
List of important preprints dealing with the ongoing coronavirus outbreak. See http://covidpreprints.com for additional resources and timeline, and https://connect.biorxiv.org/relate/content/181 for full list of bioRxiv and medRxiv preprints on this topic
| List by | Dey Lab, Zhang-He Goh |
1
SDB 78th Annual Meeting 2019
A curation of the preprints presented at the SDB meeting in Boston, July 26-30 2019. The preList will be updated throughout the duration of the meeting.
| List by | Alex Eve |
Pattern formation during development
The aim of this preList is to integrate results about the mechanisms that govern patterning during development, from genes implicated in the processes to theoritical models of pattern formation in nature.
| List by | Alexa Sadier |