Mastodawn

📰 "Microtubule end stabilisation by cooperative oligomers of Ska and Ndc80 complexes"
https://doi.org/doi:10.1038/s44318-026-00749-5
https://pubmed.ncbi.nlm.nih.gov/41862644/
#Microtubule #Mitosis

Microtubule end stabilisation by cooperative oligomers of Ska and Ndc80 complexes - The EMBO Journal

During mitosis, properly aligned chromosomes stabilise microtubule ends with the help of kinetochores to ensure timely segregation of chromosomes. Microtubule-binding components of the human outer kinetochore, such as Ndc80 and Ska complexes, are present in multiple copies and together bind several microtubule ends, creating a highly multivalent binding interface. Whereas Ndc80:Ndc80 and Ndc80:microtubule binding is crucial for interface stability, Ndc80 alone in absence of Ska is unable to support stable kinetochore-attachments. Using cryo-electron tomography, we demonstrate that oligomeric Ndc80:Ska assemblies stabilise microtubule ends against shortening by strengthening lateral contacts between tubulin protofilaments at microtubule plus-ends. We further identify a point mutation within the SKA1 microtubule-binding domain that does not affect microtubule-binding of individual Ska molecules, but does abolish Ska:Ska interactions. Finally, we report that oligomerisation of Ska, in a cooperative fashion together with the Ndc80, is necessary to maintain stable microtubule attachments both in vivo and in vitro.

SpringerLink

Rxiv mechanobio 3d ago

📰 "Development of MKI-3: A Potent and Selective MASTL Inhibitor with Improved Efficacy for Cancer Treatment"
https://doi.org/doi:10.1021/acs.jmedchem.5c03599
https://pubmed.ncbi.nlm.nih.gov/41857504/
#Microtubule #Mitosis

Rxiv mechanobio 5d ago

📰 "beta-tubulin phosphorylation by Chk1 is required for normal spindle formation during cell division"
https://doi.org/doi:10.1038/s42003-026-09862-x
https://pubmed.ncbi.nlm.nih.gov/41844775/
#CellDivision #Microtubule #Mitosis #Cell

Rxiv mechanobio Mar 16

📰 "lncRNA NORM is essential for proper chromosome segregation through the Plk1-Bub1 and Nsun2 axis."
https://www.biorxiv.org/content/10.64898/2026.03.15.711899v1?rss=1 #Mitosis #Cell

lncRNA NORM is essential for proper chromosome segregation through the Plk1-Bub1 and Nsun2 axis.

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bioRxiv

Rxiv mechanobio Mar 16

📰 "Spheroid culture remodels mitosis and the proteome in tumor cells"
https://www.biorxiv.org/content/10.64898/2026.03.12.711371v1?rss=1 #Mitosis #Cell

Spheroid culture remodels mitosis and the proteome in tumor cells

Mitosis depends on precise spindle assembly and positioning, processes influenced by cell shape, size, and microenvironment. Most mechanistic insights into mitosis come from two-dimensional (2D) monolayer cultures, which lack the spatial constraints and extracellular matrix found in tissues, leaving the influence of the tissue environment on mitosis poorly understood. Here, we combine high-resolution imaging and quantitative proteomics to compare mitosis in three-dimensional (3D) multicellular spheroids, generated by magnetic levitation, with that in 2D monolayers. Using a non-transformed cell line and three cancer cell lines from breast, bone, and ovary, we show that 3D culture reshapes mitotic cells and their spindles. Tumor spheroids exhibited a prometaphase delay together with minor chromosome alignment defects, yet chromosome segregation remained largely accurate. Cells in spheroids were rounder, and their spindles were smaller, with increased multipolarity and defects in orientation and position, which varied by cell line. Proteomic profiling revealed broad downregulation of mitotic regulators in spheroids, including kinesins (KIF11, KIF4A), spindle checkpoint proteins, and APC/C components, accompanied by enrichment of metabolic and mitochondrial pathways. Together, our results reveal both shared and cell line-specific modes of mitotic restructuring and establish a framework that connects proteome state to mitotic architecture in 3D environments. ### Competing Interest Statement The authors have declared no competing interest. European Research Council, https://ror.org/0472cxd90 Croatian Science Foundation, https://ror.org/03n51vw80 Deutsche Forschungsgemeinschaft, https://ror.org/018mejw64

bioRxiv

Rxiv mechanobio Mar 13

📰 "Novel KIF22 Variants Disrupt Mitosis in Human Chondrocytes and Expand SEMDJL2 Mechanisms"
https://www.biorxiv.org/content/10.64898/2026.03.11.711192v1?rss=1 #Mitosis #Forces #Cell

Novel KIF22 Variants Disrupt Mitosis in Human Chondrocytes and Expand SEMDJL2 Mechanisms

Spondyloepimetaphyseal dysplasia with joint laxity, type 2 (SEMDJL2) is a rare skeletal disorder caused by pathogenic variants in KIF22, a mitotic chromokinesin that generates polar ejection forces (PEF) to ensure proper chromosome alignment and segregation. Although prior work showed that SEMDJL2-associated KIF22 hotspot variants impair chromosome segregation in epithelial cells, how these variants affect chondrocyte mitosis remains incompletely understood. Here, we analyzed the effects of the hotspot variant R149Q, a recently reported recessive variant R49Q, and two newly identified heterozygous variants, P144T and E222Q, in human chondrocytes. Both novel variants were identified in individuals with classic SEMDJL2 features. P144T and E222Q retained PEF-generating activity, whereas R49Q displayed reduced PEFs, consistent with their respective inheritance patterns. Live cell imaging revealed that all variants disrupted mitosis. The heterozygous variants (P144T, E222Q, R149Q) dominantly impeded anaphase chromosome segregation and spindle pole separation, supporting reclassification of P144T and E222Q as likely pathogenic. In contrast, R49Q caused milder, partially penetrant segregation defects, consistent with reduced and dysregulated motor activity. Together, our results define two mechanistic classes of KIF22 dysregulation: constitutive activation in heterozygous variants, which fail to down‑regulate KIF22 at anaphase onset, and mixed‑state dysregulation in the recessive R49Q variant, which exhibits partial loss of polar ejection force activity coupled with incomplete inactivation during anaphase. These findings broaden the mechanistic framework for how KIF22 variants perturb mitosis in chondrocytes and expand the genotypic landscape associated with SEMDJL2. ### Competing Interest Statement The authors have declared no competing interest. National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM144133

bioRxiv

diana 🏳️‍⚧️🦋🌱Mar 10

Here we see cats dividing by mitosis

#mitosis #caturday #caturdayeveryday

Rxiv mechanobio Mar 10

📰 "CDK/mTOR-dependent phosphorylation of UBE2H restrains its charging with ubiquitin and regulates CTLH-dependent degradation"
https://www.biorxiv.org/content/10.64898/2026.03.07.710281v1?rss=1 #Mitosis #Cell

CDK/mTOR-dependent phosphorylation of UBE2H restrains its charging with ubiquitin and regulates CTLH-dependent degradation

The C-terminal to LisH (CTLH) complex is a modular multi-subunit E3 ligase with diverse biological functions, yet how its overall ubiquitylation activity is tuned remains unclear. Here, we identify CDK- and mTOR-dependent phosphorylation of the cognate E2 enzyme UBE2H as a key regulator of CTLH E3 catalytic capacity. Phosphorylation of two N-terminal serine residues (S3/S5) reduces UBE2H charging with ubiquitin, thereby limiting the pool of active E2 available to CTLH. Mitotic CDK activity inactivates UBE2H during mitosis, whereas mTOR restrains UBE2H charging in interphase to couple CTLH-dependent ubiquitylation to nutrient status. Preventing this phosphorylation maintains UBE2H charging, enhances CTLH-mediated substrate degradation, promotes CTLH subunit turnover, and causes proliferation and mitotic defects. Using hyperactive UBE2H, we identify two additional CTLH substrates, the mitotic kinase NEK9 and Angio-associated migratory cell protein (AAMP) and define a DR-like C-degron recognized by the CTLH subunit MKLN1. These findings reveal how regulation of an E2 enzyme by cell cycle and nutrient signaling pathways dynamically shape CTLH activity. ### Competing Interest Statement The authors have declared no competing interest. NIH Common Fund, https://ror.org/001d55x84, R01 GM132129, R01 GM67945

bioRxiv

Rxiv mechanobio Feb 27

📰 "KIF18B Is Essential for Lung Adenocarcinoma Progression Through the E2F Transcriptional Network"
https://doi.org/doi:10.3390/ijms27041807
https://pubmed.ncbi.nlm.nih.gov/41751942/
#Mitosis #Kinesin

Rxiv mechanobio Feb 27

📰 "Plasmodium ARK1 regulates spindle formation during atypical mitosis and forms a divergent chromosomal passenger complex"
https://doi.org/doi:10.1038/s41467-026-69460-7
https://pubmed.ncbi.nlm.nih.gov/41748607/
#Microtubule #Mitosis