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Article
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Mild replication stress causes premature centriole disengagement via a sub-critical Plk1 activity under the control of ATR-Chk1
Mild replication stress leads to premature centriole disengagement while delaying mitotic onset. Here, Dwivedi et al. demonstrate that this results from sub-critical Plk1 kinase activity, enabling centrosome cycling but impeding rapid mitotic entry.
- Devashish Dwivedi
- , Daniela Harry
- & Patrick Meraldi
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Article
| Open Access
Acentrosomal spindles assemble from branching microtubule nucleation near chromosomes in Xenopus laevis egg extract
Microtubules need to be generated during cell division to build mitotic or meiotic spindles. Here, reconstitution experiments and theoretical modeling show that chromosomes alone can trigger branching microtubule nucleation.
- Bernardo Gouveia
- , Sagar U. Setru
- & Sabine Petry
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Comment
| Open Access
Structural insights into how augmin augments the mitotic spindle
Cell division critically requires amplification of microtubules (MTs) in the bipolar mitotic spindle. This relies on the filamentous augmin complex that enables MT branching. Studies by Gabel et al., Zupa et al. and Travis et al. describe consistent integrated atomic models of the extraordinarily flexible augmin complex. Their work prompts the question: what is this flexibility really needed for?
- Szymon W. Manka
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Article
| Open Access
Integrated model of the vertebrate augmin complex
Many microtubules in the mitotic spindle are made through microtubule branching. Here, the authors report a structural model of the augmin complex and insights into its role in microtubule branching.
- Sophie M. Travis
- , Brian P. Mahon
- & Sabine Petry
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Article
| Open Access
Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
Mitotic spindle assembly is not fully understood. This work reveals that kinetochores drive the coarsening of a uniform microtubule array into bundles, which promote spindle formation and chromosome segregation fidelity.
- Jurica Matković
- , Subhadip Ghosh
- & Iva M. Tolić
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Article
| Open Access
Chromosome segregation fidelity requires microtubule polyglutamylation by the cancer downregulated enzyme TTLL11
The authors show that polyglutamylation of spindle microtubules is essential for error-free chromosome segregation and is mediated through Tubulin Tyrosine Ligase Like 11 (TTLL11), which is found to be frequently downregulated in cancer.
- Ivan Zadra
- , Senda Jimenez-Delgado
- & Isabelle Vernos
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Article
| Open Access
The augmin complex architecture reveals structural insights into microtubule branching
The formation of branched microtubule networks in mitotic spindles depends on the augmin complex. Zupa, Würtz et al. elucidate the molecular architecture and conformational plasticity of the augmin complex using integrative structural biology, providing structural insights into microtubule branching.
- Erik Zupa
- , Martin Würtz
- & Stefan Pfeffer
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Article
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Molecular architecture of the augmin complex
The eight-subunit augmin complex is required to nucleate branching microtubules and create a robust mitotic spindle during cell division. Here, the authors use cryo-EM, crosslinking mass spectrometry, and computational tools to build a structural model of the human augmin complex.
- Clinton A. Gabel
- , Zhuang Li
- & Leifu Chang
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Article
| Open Access
Evidence for a HURP/EB free mixed-nucleotide zone in kinetochore-microtubules
Microtubules are built from GDP-tubulin lattices with small GTP caps at their plus-ends. Here, the authors reveal that microtubules that attach to kinetochores in mitosis contain, in addition to the GTP-cap and the GDP-lattices, a dynamic micron-sized mixed-nucleotide zone.
- Cédric Castrogiovanni
- , Alessio V. Inchingolo
- & Patrick Meraldi
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Article
| Open Access
The HHIP-AS1 lncRNA promotes tumorigenicity through stabilization of dynein complex 1 in human SHH-driven tumors
Long non-coding RNAs (lncRNAs) can contribute to cancers that are driven by Sonic hedgehog (SHH) signaling. Here the authors report that lncRNA HHIP-AS1 stabilises the mRNA of dynein complex 1, thereby, promoting the pro-mitotic effects of SHH-driven tumors.
- Jasmin Bartl
- , Marco Zanini
- & Marc Remke
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Article
| Open Access
Cortical Cyclin A controls spindle orientation during asymmetric cell divisions in Drosophila
The Frizzled/Dishevelled planar cell polarity pathway is involved in mitotic spindle orientation, but how this is coordinated with the cell cycle is unclear. Here, the authors show with Drosophila sensory organ precursor cells that Cyclin A is recruited in prophase by Frizzled/Dishevelled, regulating division orientation.
- Pénélope Darnat
- , Angélique Burg
- & Agnès Audibert
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Article
| Open Access
Spindle motility skews division site determination during asymmetric cell division in Physcomitrella
In plants, the site of asymmetric cell division (ACD) is generally thought to be determined by the preprophase band and the mitotic spindle is typically static. However, the authors show here that the moss Physcomitrella has motile mitotic spindles that can skew ACD in the absence of preprophase bands.
- Elena Kozgunova
- , Mari W. Yoshida
- & Gohta Goshima
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Article
| Open Access
Vasa nucleates asymmetric translation along the mitotic spindle during unequal cell divisions
Association of mRNA translation with the mitotic spindle is thought to be involved in localized production of cell fate determinants. Here, the authors show Vasa facilitates asymmetric translation, which contributes to differential regulation during sea urchin embryogenesis.
- Ana Fernandez-Nicolas
- , Alicia Uchida
- & Mamiko Yajima
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Article
| Open Access
Recruitment of two Ndc80 complexes via the CENP-T pathway is sufficient for kinetochore functions
The kinetochores contain multiple protein interaction networks. Takenoshita et al. analyzed the complicated networks using the genetic method and revealed that two copies of Ndc80 complexes on CENP-T are sufficient for kinetochore functions.
- Yusuke Takenoshita
- , Masatoshi Hara
- & Tatsuo Fukagawa
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Article
| Open Access
NuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation
Mitotic spindle assembly is required for proper cell division, but many underlying mechanisms remain unclear. Here, the authors show that NuMa undergoes liquid-liquid phase separation, condensing on spindle poles during mitotic entry and enriching critical components to promote spindle assembly.
- Mengjie Sun
- , Mingkang Jia
- & Chuanmao Zhang
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Article
| Open Access
Counteraction between Astrin-PP1 and Cyclin-B-CDK1 pathways protects chromosome-microtubule attachments independent of biorientation
Chromosome instability frequently occurs due to issues with chromosome-microtubule attachments. Here the authors show that the Astrin-PP1 and Cyclin-B-CDK1 pathways counteract each other to protect chromosome-microtubule attachments independent of biorientation.
- Xinhong Song
- , Duccio Conti
- & Viji M. Draviam
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Article
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Prc1-rich kinetochores are required for error-free acentrosomal spindle bipolarization during meiosis I in mouse oocytes
Oocyte meiosis must achieve spindle bipolarization without predefined spatial cues. Yoshida et al. demonstrate that spindle bipolarization during meiosis I in mouse oocytes requires kinetochores to prevent chromosome segregation errors, a phenomenon that does not occur in error-prone human oocytes.
- Shuhei Yoshida
- , Sui Nishiyama
- & Tomoya S. Kitajima
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Article
| Open Access
The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis
The midbody is an organelle present at the bridge connecting two cells at the end of cell division. Here, the authors use mass spectrometry to define the midbody interactome and uncover a role for PP1 phosphatases in microtubule dynamics and regulation of cytokinesis.
- Luisa Capalbo
- , Zuni I. Bassi
- & Pier Paolo D’Avino
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Article
| Open Access
DNA double-strand breaks in telophase lead to coalescence between segregated sister chromatid loci
The mechanism regulating DNA repair in late anaphase or telophase is not yet clear. Here authors reveal that DNA double strand breaks in telophase causes a partial reversal of sister chromosome segregation which could create an opportunity of using the sister for repair in telophase.
- Jessel Ayra-Plasencia
- & Félix Machín
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Article
| Open Access
Live imaging screen reveals that TYRO3 and GAK ensure accurate spindle positioning in human cells
Correct spindle positioning is critical for cell division but the full set of proteins regulating this is unclear. Here, with a live imaging siRNA-based screen in human cells, the authors identify 16 candidates required for this process, 11 of which were previously unassociated with such a function, including TYRO3 and GAK.
- Benita Wolf
- , Coralie Busso
- & Pierre Gönczy
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Article
| Open Access
Centromere mechanical maturation during mammalian cell mitosis
During mitosis, tension at the centromere occurs from the spindle but the role of centromere mechanics in controlling metaphase tension is poorly understood. Here, the authors report that mechanical stiffnness of the centromere matures during mitotic progression and is amplified specifically at metaphase.
- Lauren A. Harasymiw
- , Damien Tank
- & Melissa K. Gardner
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Article
| Open Access
The mitotic spindle is chiral due to torques within microtubule bundles
Forces are required for congression of chromosomes by microtubule spindles. Here, using super-resolution microscopy and computational modelling, the authors find that in addition to forces, torques caused by the microtubule motor protein kinesin-5 induce chirality and curves into the spindle.
- Maja Novak
- , Bruno Polak
- & Nenad Pavin
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Article
| Open Access
Microtubule minus-end aster organization is driven by processive HSET-tubulin clusters
Microtubules (MT) form higher-order structures such as asters, but the molecular pathway underlying aster formation remains unclear. Here authors demonstrate that the kinesin-14, HSET, clusters with soluble (nonMT) tubulin via its N-terminal tail domain and thereby promotes MT aster formation.
- Stephen R. Norris
- , Seungyeon Jung
- & Ryoma Ohi
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Article
| Open Access
Complete microtubule–kinetochore occupancy favours the segregation of merotelic attachments
Single microtubules (MTs) can move chromosomes, but it is unclear why kinetochores bind up to 20 MTs. Here, the authors decrease the number of kinetochore MTs with BAL27862 and see lagging chromosomes, suggesting that numerous kinetochore MTs provide force ensuring robust chromosomal segregation.
- Damian Dudka
- , Anna Noatynska
- & Patrick Meraldi
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Article
| Open Access
Uncovering the balance of forces driving microtubule aster migration in C. elegans zygotes
Microtubule asters are positioned precisely within cells by forces generated by molecular motors, but it is unclear how these are integrated in space and time. Here the authors perform in vivo drag measurements and genetic manipulations to determine the balance of forces that position microtubule asters in C. elegans zygotes.
- A. De Simone
- , A. Spahr
- & P. Gönczy
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Article
| Open Access
Unattached kinetochores drive their own capturing by sequestering a CLASP
Kinetochores (KT) that are not attached to microtubules prevent chromosome missegregation via the spindle assembly checkpoint. Here the authors show that Mps1 localizes Stu1 at unattached KTs together with Slk19, causing a reorganization of the nuclear MT network that favors the capturing of unattached KT.
- Caroline Kolenda
- , Jennifer Ortiz
- & Johannes Lechner
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Article
| Open Access
Kif2 localizes to a subdomain of cortical endoplasmic reticulum that drives asymmetric spindle position
Early ascidian embryos have a cortical subdomain of endoplasmic reticulum (ER) that controls asymmetric spindle positioning driving unequal cell division. Here the authors show that the microtubule depolymerase Kif2 is localized to a cortical subdomain of the ER that is involved in asymmetric spindle positioning.
- Vlad Costache
- , Celine Hebras
- & Alex McDougall
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Article
| Open Access
Human microcephaly protein RTTN interacts with STIL and is required to build full-length centrioles
Mutations in many centriolar protein-encoding genes cause primary microcephaly. Here the authors show that human microcephaly protein RTTN directly interacts with STIL and acts downstream of STIL-mediated centriole assembly, contributing to building full-length centrioles
- Hsin-Yi Chen
- , Chien-Ting Wu
- & Tang K. Tang
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Article
| Open Access
Precocious centriole disengagement and centrosome fragmentation induced by mitotic delay
The spindle assembly checkpoint delays mitotic progression until sister chromatids are bi-oriented. Here the authors show that moderate delays in mitotic progression induce centrosome fragmentation and centriole disengagement and that spindle bipolarity is ensured by HSET-mediated spindle pole clustering.
- Menuka Karki
- , Neda Keyhaninejad
- & Charles B. Shuster
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Article
| Open Access
Kinesin-5-independent mitotic spindle assembly requires the antiparallel microtubule crosslinker Ase1 in fission yeast
Bipolar spindle assembly requires a balance of kinesin 14 pulling and kinesin 5 pushing forces. Here, the authors show that in fission yeast, spindle formation can occur in the absence of kinesin 5 (Cut7) and 14 (Pkl1) but requires the microtubule-associated protein Ase1 for spindle bipolarity.
- Sergio A. Rincon
- , Adam Lamson
- & Phong T. Tran
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Article
| Open Access
C. elegans chromosomes connect to centrosomes by anchoring into the spindle network
A connection between centrosomes and chromosomes is a key feature of mitotic spindles. Here the authors generate 3D reconstructions of whole mitotic spindles in earlyC. elegansembryos and show that chromosomes are anchored by the entire spindle network and that connections through kinetochore microtubules are few and likely very transient.
- Stefanie Redemann
- , Johannes Baumgart
- & Thomas Müller-Reichert
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Article
| Open Access
Stat3 regulates centrosome clustering in cancer cells via Stathmin/PLK1
Cancer cells have amplified centrosomes and deal with this abnormality by clustering them together so that they can be segregated in daughter cells. Here the authors perform a screening looking for inhibitors of this clustering process and find that STAT3 regulates this process independently of its transcriptional function.
- Edward J. Morris
- , Eiko Kawamura
- & Shoukat Dedhar
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Article
| Open Access
DNA replication licensing factor Cdc6 and Plk4 kinase antagonistically regulate centrosome duplication via Sas-6
Centrosome duplication is synchronized with cell cycle events but how this is regulated at a molecular level is unclear. Here, the authors show that the DNA replication licensing factor Cdc6 restrains centrosome duplication via binding and inhibiting Sas-6, and the inhibition of Cdc6 on Sas-6 is negatively regulated by Plk4 phosphorylation.
- Xiaowei Xu
- , Shijiao Huang
- & Chuanmao Zhang
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Article
| Open Access
Cell division orientation is coupled to cell–cell adhesion by the E-cadherin/LGN complex
Cell–cell adhesion and oriented cell division play key roles in tissue architecture, but how they are coordinated is not known. Here, the authors show that E-cadherin interacts with LGN, and thereby provides a cortical cue that serves to stabilize cortical attachment of astral microtubules at cell–cell adhesions, thus orienting the mitotic spindle.
- Martijn Gloerich
- , Julie M. Bianchini
- & W. James Nelson
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Article
| Open Access
Interphase adhesion geometry is transmitted to an internal regulator for spindle orientation via caveolin-1
Studies imply that cell adhesion geometry during interphase dictates the orientation of the cell division axis. Here the authors show that accumulation of caveolin-1 to rapidly retracting regions during cell rounding sets the spindle orientation by recruiting Gαi1-LGN-NuMA to the cortex.
- Shigeru Matsumura
- , Tomoko Kojidani
- & Fumiko Toyoshima
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Article
| Open Access
A CEP215–HSET complex links centrosomes with spindle poles and drives centrosome clustering in cancer
Centrosome clustering allows survival of cells with amplified centrosomes at the cost of chromosome instability. Here, Chavali et al. show that the centrosome component CEP215 collaborates with the kinesin motor HSET both to maintain spindle poles connections and to cluster centrosomes.
- Pavithra L. Chavali
- , Gayathri Chandrasekaran
- & Fanni Gergely
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Article
| Open Access
A ligand-independent integrin β1 mechanosensory complex guides spindle orientation
During cell division, the orientation of the mitotic spindle is sensitive to forces exerted on the cell cortex. Here Petridou and Skourides show that such cues are sensed by a mechanosensory complex established on force activated integrin β1 independent of ligand binding.
- Nicoletta I. Petridou
- & Paris A. Skourides
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Article
| Open Access
The Bub1–Plk1 kinase complex promotes spindle checkpoint signalling through Cdc20 phosphorylation
The mitotic checkpoint complex (MCC) inhibits the anaphase-promoting complex (APC/C) bound to Cdc20 in response to spindle defects. Here, the authors show that Bub1-Plk1-mediated phosphorylation of Cdc20 constitutes a parallel, non-redundant APC/C-inhibitory mechanism in addition to MCC activity.
- Luying Jia
- , Bing Li
- & Hongtao Yu
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Article
| Open Access
Kinetochore–microtubule attachment is sufficient to satisfy the human spindle assembly checkpoint
The spindle assembly checkpoint protects against premature chromosome segregation during mitosis but it is not known whether microtubule attachment to the kinetochore, or force generated from this interaction, is being monitored. Here the authors uncouple these processes and show that microtubule attachment is sufficient to satisfy the checkpoint.
- Banafsheh Etemad
- , Timo E. F. Kuijt
- & Geert J. P. L. Kops
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Article
| Open Access
Kinesin-5 is a microtubule polymerase
Kinesin-5 is a tetrameric motor that slides antiparallel microtubules during mitotic spindle assembly. Chen and Hancock show that this motor also promotes microtubule assembly by stabilising protofilaments at growing plus ends, which results in the formation of banana peel-like structures.
- Yalei Chen
- & William O Hancock
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Article
| Open Access
JAM-A regulates cortical dynein localization through Cdc42 to control planar spindle orientation during mitosis
Polarized epithelial cells orient their mitotic spindles in the plane of the sheet but the role of cell adhesion molecules in this process is poorly understood. Here Tuncay et al. show that JAM-A regulates spindle orientation by creating a gradient of PtdIns(3,4,5)P3, regulating cortical actin assembly and localizing dynactin to the cell cortex.
- Hüseyin Tuncay
- , Benjamin F. Brinkmann
- & Klaus Ebnet
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Article
| Open Access
An epigenetic regulator emerges as microtubule minus-end binding and stabilizing factor in mitosis
The heptameric KAT8-associated nonspecific lethal complex consists of highly conserved chromatin modifier proteins. Here, the authors show a role for the members of the complex in regulating microtubule assembly during mitosis.
- Sylvain Meunier
- , Maria Shvedunova
- & Asifa Akhtar
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Article
| Open Access
Direct interaction between centralspindlin and PRC1 reinforces mechanical resilience of the central spindle
The central spindle is an anti parallel bundle of microtubules that forms between segregating chromosomes and links the two halves of the mitotic spindle. Lee et al.reveal that interaction between two microtubule bundling proteins at the central spindle confers robustness to cortical pulling forces.
- Kian-Yong Lee
- , Behrooz Esmaeili
- & Masanori Mishima
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Article
| Open Access
Cdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation
Centrosome separation, promoted by the kinesin Eg5, is antagonized by the guanine nucleotide exchange factor Tiam1 through an unknown mechanism. Here Whalley et al. show that Tiam1 is phosphorylated by cyclin-dependent kinase 1 in prophase, leading to downstream activation of p21-activated kinases (PAKs).
- Helen J. Whalley
- , Andrew P. Porter
- & Angeliki Malliri
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Article
| Open Access
Asymmetrically dividing Drosophila neuroblasts utilize two spatially and temporally independent cytokinesis pathways
In asymmetrically dividing cells, both spindle-dependent and spindle-independent cleavage furrow positioning pathways are involved in cytokinesis. Here the authors find that Survivin and the mitotic spindle are required to stabilize the position of the cleavage furrow and to complete cytokinesis in Drosophilaneuroblasts.
- Michaela Roth
- , Chantal Roubinet
- & Clemens Cabernard
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A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte
Asymmetric spindle positioning in female mouse meiosis depends on the assembly of actin networks. Here, Chaigne et al. show by theoretical modelling and artificial manipulation of the oocyte cortex that a narrow stiffness regime is required to correctly position the spindle during meiosis I in the mouse oocyte.
- A. Chaigne
- , C. Campillo
- & M. E. Terret
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FAK transduces extracellular forces that orient the mitotic spindle and control tissue morphogenesis
Orientation of the mitotic spindle is influenced by extracellular forces acting on the cell cortex. Here Petridou et al.identify FAK as a key transducer of mechanical forces in this context and as a result is a key regulator of spindle orientation controlling tissue architecture and morphogenesis.
- Nicoletta I. Petridou
- & Paris A. Skourides
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Spatial-temporal model for silencing of the mitotic spindle assembly checkpoint
During cell division, a single chromosome that lacks attachment to microtubules is sufficient to delay chromosome segregation. Chen and Liu construct a model demonstrating that the transport of regulators along microtubules may explain the remarkable sensitivity and robustness of this checkpoint.
- Jing Chen
- & Jian Liu
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The nucleoporin MEL-28 promotes RanGTP-dependent γ-tubulin recruitment and microtubule nucleation in mitotic spindle formation
On mitotic exit, the nucleoporin MEL-28 binds to chromatin and seeds the formation of nuclear pore complexes. Here Yokoyama et al.show that upon mitotic entry, MEL-28 re-localizes to microtubules where it functions in assembling the mitotic spindle, revealing roles for MEL-28 throughout the cell cycle.
- Hideki Yokoyama
- , Birgit Koch
- & Oliver J. Gruss
Ran-GTP assembles a specialized spindle structure for accurate chromosome segregation in medaka early embryos