bims-micesi Biomed News
on Mitotic cell signalling
Issue of 2025–08–31
twenty-two papers selected by
Valentina Piano, Uniklinik Köln
  1. Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex.
  2. A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.
  3. Branching, crosslinking and decentralization of microtubules accelerates intracellular assembly.
  4. Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation.
  5. Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer.
  6. Use of Nucleoporin-Conjugated Beads to Study the Nuclear Pore Complex Assembly on the Nuclear Membrane.
  7. The cAMP-PKA signaling initiates mitosis by phosphorylating Bora.
  8. Functional characterization of the Csm1-like protein TITAN 9 in Arabidopsis thaliana.
  9. HDAC6-dependent deacetylation of SAE2 enhances SUMO1 conjugation for mitotic integrity.
  10. Dual mitotic bookmarking by GAF and H3K27ac orchestrates differential propagation of cell fate memory in neural development.
  11. Quantifying Nuclear Shape Fluctuations During Early Mitosis.
  12. The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells.
  13. Histone H3 N-Terminal Tail Residues Important for Meiosis in Saccharomyces cerevisiae.
  14. MRE11 orchestrates porcine oocyte meiotic progression by modulating the spindle assembly checkpoint.
  15. Maspin/SerpinB5 is a cytoskeleton-binding protein that regulates epithelial cell shape.
  16. Decoding Mitotic Chromosome Assembly: Three Rules Governing Condensin-Cohesin Engagement.
  17. Dynamic remodeling of centrioles and the microtubule cytoskeleton in the lifecycle of chytrid fungi.
  18. Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells.
  19. PLK1 inhibitors for the treatment of colorectal cancer.
  20. Fast Super-Resolution Live Cell Imaging of Nuclear Membrane-Endoplasmic Reticulum Dynamics.
  21. Epsin1 enforces a condensation-dependent checkpoint for ubiquitylated cargo during clathrin-mediated endocytosis.
  22. Mechanistic modeling of mitosis: Insights from three collaborative case studies.
  1. Nat Commun. 2025 Aug 22. 16(1): 7832
    Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex.
    María Fernández-Casañas, Eleftheria Karanika, Umit Aliyaskarova, Tomisin Olukoga, Alex D Herbert, Antony W Oliver, Matthew Day, Adrijana Crncec, Kok-Lung Chan.
      The BTRR (BLM/TOP3A/RMI1/RMI2) complex resolves DNA replication and recombination intermediates to maintain genome stability. Alongside PICH, they target mitotic DNA intertwinements, known as ultrafine DNA bridges, facilitating chromosome segregation. Both BLM and PICH undergo transient mitotic hyper-phosphorylation, but the biological significance of this remains elusive. Here, we uncover that during early mitosis, CDK1 and PLK1 constrain BTRR complex activities at centromeres. CDK1 destabilises the complex, limiting its binding to PICH at specialised chromatin underneath kinetochores. Inactivating the BLM-TOP3A interaction compromises the UFB-binding complex functions and prevents centromere destruction. Different phosphorylation on BLM affects the TRR subcomplex interaction and the mitotic activity, particularly phosphorylation at Ser144 and multiple PLK1-target sites suppresses illegitimate centromeric DNA unwinding. However, unleashing such activity after sister-chromatid cohesion inactivation facilitates the separation of entangled chromosomes. Here, we show a centromere protection pathway in human mitotic cells, heavily reliant on a tight spatiotemporal control of the BTRR complex.
    DOI:  https://doi.org/10.1038/s41467-025-62966-6
  2. Dis Model Mech. 2025 Aug 01. pii: dmm052409. [Epub ahead of print]18(8):
    A novel MAP7D1 mutation causes mitotic defects and RPS14 accumulation in Shwachman-Diamond syndrome patient cells.
    Seren Kucukvardar, Arzu Karabay.
      The importance of microtubule stability and microtubule-associated proteins in the etiology of Shwachman-Diamond syndrome (SDS) has been highlighted in recent studies. In one patient with SDS, a novel MAP7D1:c.601C>T, p.R201W variant has been identified. In this study, the causality of this variant in the pathogenesis of SDS was investigated. Mutation in the microtubule-binding domain of MAP7D1 caused disruption of its interaction with microtubules. SDS fibroblasts exhibited a decreased cell size with reduced microtubule density, and mitotic defects, including multipolar or bipolar unstable spindles, lagging chromosomes, and shortened inter-centrosomal distance. Additionally, ribosomal protein S14 (RPS14) accumulated within incorrectly dividing SDS fibroblasts. To further evaluate whether these abnormalities are directly attributable to the MAP7D1 mutation, mitotic processes were investigated through genetic manipulations of MAP7D1 in T98G glioblastoma and HEK293T embryonic kidney cell lines. Consistent with data from SDS fibroblasts, similar phenotypes were detected upon overexpression of mutant MAP7D1 and depletion of MAP7D1. Our findings revealed that the MAP7D1 mutation acts as a loss-of-function mutation and contributes to SDS pathogenesis by disrupting microtubule dynamics and ribosomal protein regulation, identifying MAP7D1 as a gene with substantial impact for SDS.
    Keywords:  MAP7D1; Microtubule; Mitotic spindle; RPS14; Shwachman−Diamond syndrome
    DOI:  https://doi.org/10.1242/dmm.052409
  3. Biophys J. 2025 Aug 20. pii: S0006-3495(25)00528-4. [Epub ahead of print]
    Branching, crosslinking and decentralization of microtubules accelerates intracellular assembly.
    Apurba Sarkar, Alex Mogilner, Raja Paul.
      Before cell division, mitotic spindle is assembled from chromosomes and centrosomes. After the cell division, Golgi organelles assemble from multiple vesicles scattered across daughter cells. These are among many other examples of intracellular assembly of vesicles, organelles and chromosomes made possible by dynamic microtubules. The most prominent microtubule networks are centrosome-focused asters that 'search' for the vesicles and chromosomes, but there are also microtubules originating from the vesicles and chromosomes, raising the question whether a coordination between multiple microtubule networks optimizes the assembly process. This study uses a computational model to examine how microtubule dynamics influence the assembly of organelles from vesicles. The model includes two microtubule populations: microtubules anchored to the vesicles, which drive local clustering, and 'central' microtubules anchored to the centrosome that aggregate the vesicles globally. Simulations show that a microtubule decentralization - balanced contribution from both microtubule populations - accelerates the assembly of tens of vesicles, but that assigning all microtubules to hundreds of vesicles optimizes the assembly. Directionally biased microtubule growth, particularly when avoiding spontaneous catastrophe events, further accelerates the assembly. Additionally, microtubule branching, when occurring at optimal angles and spacings, enhances the assembly's efficiency. Lastly, rapid crosslinking of overlapping central and 'local' microtubules can drastically accelerate the assembly. Applying this model to the spindle assembly in early mitosis reveals similar insights. The model suggests that the observed multiple microtubule networks optimize the intracellular assembly processes when molecular resources are limited.
    DOI:  https://doi.org/10.1016/j.bpj.2025.08.016
  4. EMBO Rep. 2025 Aug 20.
    Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation.
    Tappei Mishina, Aurélien Courtois, Shuhei Yoshida, Kohei Asai, Hiroshi Kiyonari, Tomoya S Kitajima.
      Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in acentrosomal spindle bipolarization and homologous chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region, where merotelic kinetochore-microtubule attachments are favored to form. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and reveal a spatially differential requirement for homologous chromosome biorientation within the spindle.
    Keywords:  Chromosome Segregation; Meiosis; Oocyte; Spindle
    DOI:  https://doi.org/10.1038/s44319-025-00539-w
  5. Life Sci Alliance. 2025 Nov;pii: e202503295. [Epub ahead of print]8(11):
    Wnt10b signaling regulates replication stress-induced chromosomal instability in human cancer.
    Alexander Haas, Friederike Wenz, Janina Hattemer, Janine Wesslowski, Gary Davidson, Oksana Voloshanenko, Michael Boutros, Sergio P Acebron, Holger Bastians.
      Wnt signaling pathways are involved in various developmental and tissue maintenance functions, whereas deregulated Wnt signaling is closely linked to human cancer. Recent work revealed that loss of Wnt signaling impairs mitosis and causes abnormal microtubule growth at the mitotic spindle resulting in chromosome missegregation and aneuploidy, both of which are hallmarks of cancer cells exhibiting chromosomal instability (CIN). Here, we show that upon DNA replication stress, a condition typically associated with CIN, Wnt10b acts to prevent increased microtubule dynamics from the S phase until mitosis, thereby ensuring faithful chromosome segregation. Interestingly, replication stress-induced chromosomal breaks are also efficiently suppressed by Wnt10b. Thus, our results show that Wnt10b signaling regulates replication stress-induced chromosome missegregation and breakage, and hence is a determinant for broad genome instability in cancer cells.
    DOI:  https://doi.org/10.26508/lsa.202503295
  6. Methods Mol Biol. 2025 ;2958 169-181
    Use of Nucleoporin-Conjugated Beads to Study the Nuclear Pore Complex Assembly on the Nuclear Membrane.
    Şükriye Bilir, Yasushi Hiraoka, Tokuko Haraguchi.
      Reassembly of the nuclear pore complex (NPC) at the end of mitosis is a key event for establishing a functional nuclear envelope. However, the role of each NPC component (Nup) in NPC reassembly remained unclear. Here, we describe a method using artificial beads conjugated with an anti-GFP antibody. In this method, such beads are introduced into living cells expressing the Nup of interest fused with GFP to tether the specific Nup around the beads. By examining the Nup-conjugated beads in mitotic telophase cells, it is possible to investigate the role of the specific Nup of interest in NPC formation on the nuclear membrane.
    Keywords:  Anti-GFP antibody-conjugated bead; Live CLEM imaging; Live-cell imaging; Nuclear pore complex; Nucleoporin; Nup-bead
    DOI:  https://doi.org/10.1007/978-1-0716-4714-1_12
  7. Nat Commun. 2025 Aug 24. 16(1): 7898
    The cAMP-PKA signaling initiates mitosis by phosphorylating Bora.
    Min Zhu, Shinan Zhou, Yingqi Zhang, Qinfu Chen, Xueying Yuan, Long Zhang, Haiyan Yan, Fangwei Wang.
      Timely entry into mitosis requires activation of Polo-like kinase 1 (Plk1) by Aurora kinase A (Aurora A), but the upstream signaling trigger remains unclear. Here, we show that cyclic AMP (cAMP) signaling serves as a critical initiator of mitosis in mammalian cells. Specifically, the cAMP-dependent protein kinase (PKA) phosphorylates Bora, enabling it to bind Aurora A and recruit it to the Bora-Plk1 complex during G2 phase, thereby facilitating Aurora A-dependent activation of Plk1. Disruption of PKA-mediated Bora phosphorylation or the Bora-Aurora A interaction impairs Plk1 activation and delays the G2-to-mitosis (G2/M) transition. Conversely, a phospho-mimetic Bora mutant bypasses the requirement for PKA in promoting Bora-Aurora A interaction, Plk1 activation, and mitotic entry. Furthermore, PKA-mediated Bora phosphorylation and the resulting Bora-Aurora A interaction are essential for mitotic entry during DNA damage checkpoint recovery. Together, these findings identify the cAMP-PKA-Bora-Aurora A-Plk1 signaling cascade as a previously unrecognized and critical trigger for mitotic commitment.
    DOI:  https://doi.org/10.1038/s41467-025-63352-y
  8. iScience. 2025 Sep 19. 28(9): 113251
    Functional characterization of the Csm1-like protein TITAN 9 in Arabidopsis thaliana.
    Zhijian Zhang, Franziska Böwer, Shinichiro Komaki, Aladár Pettkó-Szandtner, Anastasiia O Skuba, Eelco C Tromer, Zoltán Magyar, Maren Heese, Arp Schnittger.
      Kinetochores are essential for chromosome segregation in eukaryotes. An important component of kinetochores in opisthokonta is Csm1. However, its function appears to be diversified and, while Csm1 in budding yeast is a component of the monopolin complex mediating mono-orientation of sister kinetochores during meiosis I, the fission yeast homolog Pcs1 prevents merotelic spindle microtubule attachments during mitosis and meiosis II. Here, we have characterized TITAN9 (TTN9), a distantly related Csm1-like protein in the flowering plant Arabidopsis. TTN9 accumulates in mitotic and meiotic tissue and localizes to centromeres throughout the cell cycle. By analyzing proteome-wide TTN9 associated proteins, we identified a substantial subset of the Arabidopsis kinetochore proteome, including DSN1, mirroring known Csm1 interactions in yeast. While homozygous ttn9 mutants are not viable, a meiosis-specific knock-down of TTN9 causes chromosome segregation defects and split centromeres during meiosis I. These findings suggest that Csm1-like proteins contribute to conserved kinetochore functions across eukaryotes.
    Keywords:  plant Biology; plant bioinformatics; plant development; plant evolution; plant genetics; plant physiology; plant systematics
    DOI:  https://doi.org/10.1016/j.isci.2025.113251
  9. EMBO J. 2025 Aug 20.
    HDAC6-dependent deacetylation of SAE2 enhances SUMO1 conjugation for mitotic integrity.
    Alexander J Lanz, Alexandra K Walker, Mohammed Jamshad, Alexander J Garvin, Matthew Stewart, Peter Wotherspoon, Benjamin F Cooper, Matthew Mackintosh, Oliver Crutchley, Timothy J Knowles, Joanna R Morris.
      Mammalian cells express three conjugatable SUMO variants: SUMO1 and the closely related SUMO2 and SUMO3 (together referred to as SUMO2/3). While some substrates are modified by both, others show a clear preference, though the basis for this selectivity remains unclear. Here, we examine a modification of the catalytic component of the human SUMO activation enzyme, SAE2. We find that lysine 164 of SAE2 undergoes HDAC6-dependent deacetylation during mitosis. A non-deacetylatable acetyl-mimetic mutant, SAE2-K164Q, selectively enhances SUMO2 over SUMO1 activation and conjugation, and distinguishes between SUMO1 and SUMO2/3 based on differences in their C-terminal tails. Complementation of SAE2-deficient or inhibited cells with SAE2-K164Q suppresses mitotic SUMO1 conjugation and promotes multipolar spindle formation. We identify NuMA as a SUMO E1-dependent substrate and demonstrate that mitotic defects caused by SAE2-K164Q or HDAC6 inhibition are rescued by SUMO1 overexpression or expression of a GFP-SUMO1-NuMA-K1766R fusion. These results support a model in which SAE1:SAE2 deacetylation during early mitosis promotes SUMO1 conjugation to ensure mitotic fidelity, highlighting a regulatory role for the SUMO-activating enzyme in the selection of SUMO proteins.
    Keywords:  Acetylation; E1; HDAC; Mitosis; SUMOylation
    DOI:  https://doi.org/10.1038/s44318-025-00532-y
  10. Nat Commun. 2025 Aug 25. 16(1): 7930
    Dual mitotic bookmarking by GAF and H3K27ac orchestrates differential propagation of cell fate memory in neural development.
    Rulan Zhang, Jie Liu, Zimo Zhang, Zili Chen, Tanpeng Wang, Yuying Shen, Zejun Lan, Jingyi Chu, Haoxuan Tang, Xiyue Zhang, Yan Song.
      In brain development, neural stem cells (NSCs) undergo asymmetric cell divisions to replicate themselves and meanwhile produce differentiating siblings. It remains obscure how NSCs preserve their self-renewing fate across mitosis. Even less is known how cell fate memory is differentially propagated to sibling daughter cells adopting distinct cell fates. Here we found that key differentiation genes are dually bookmarked by pioneer factor GAF (GAGA factor) and H3K27ac in asymmetrically-dividing Drosophila central brain NSCs. In daughter cells adopting NSC fate, GAF promotes self-renewal through timely inhibiting differentiation genes via HDAC1-mediated H3K27 deacetylation, whereas in sibling daughter cells adopting neural progenitor fate, GAF occupancy is replaced by competitor SWI/SNF complex, allowing retention of H3K27ac mark and fast activation of differentiation genes. Thus, our study unveils a paradigm by which cell fate memory can be differentially transmitted to sibling daughter cells via dual antagonistic mitotic bookmarking and selective molecular competition mechanism.
    DOI:  https://doi.org/10.1038/s41467-025-62974-6
  11. Methods Mol Biol. 2025 ;2958 151-158
    Quantifying Nuclear Shape Fluctuations During Early Mitosis.
    Viola Introini, Giancarlo Porcella, Gururaj Rao Kidiyoor, Pietro Cicuta, Marco Cosentino Lagomarsino.
      This chapter presents a detailed methodology for monitoring nuclear shape fluctuations and their correlation with chromatin condensation, developed for our analyses of early prophase, but applicable to other contexts. Nuclear shape dynamics play a key role in mitotic progression, and understanding the mechanical and biophysical properties associated with the fast-paced fluctuations may offer insights into key cellular processes like chromatin condensation and nuclear envelope breakdown. By employing live-cell imaging and computational analysis such as segmentation and flickering spectroscopy techniques, this approach leverages high-resolution temporal tracking of nuclear shape changes during cell cycle progression to derive insights into the mechanical forces driving chromatin condensation and nuclear envelope instabilities leading to the nuclear envelope breakdown. The experimental protocol provides a step-by-step guide for synchronizing HeLa cells at a specific cell-cycle transition and manipulating chromatin condensation and cytoskeletal structures through pharmacological perturbations. The data analysis section includes methods for extracting relevant biophysical parameters, such as nuclear effective tension and nuclear invaginations, as well as image-processing analysis, to correlate nuclear deformations with chromatin dynamics. We hope this robust and accessible workflow will serve as a powerful tool for exploring the mechanical coupling between chromatin condensation and nuclear structure across different conditions, which is crucial for our fundamental understanding of the nuclear function, as well as relevant for diseases resulting in nuclear abnormalities and disrupted cellular functions.
    Keywords:  Chromatin condensation; Live-cell imaging; Mitotic progression; Nuclear envelope breakdown; Nuclear mechanics; Nuclear shape fluctuations; Prophase
    DOI:  https://doi.org/10.1007/978-1-0716-4714-1_10
  12. Nat Commun. 2025 Aug 27. 16(1): 8016
    The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells.
    Róbert Zach, Michael Annis, Sandra M Martin-Guerrero, Abdulrahman Alatawi, Kim Hou Chia, Megan Meredith, Kay Osborn, Nisha Peter, William Pearce, Jessica Booth, Mohan Rajasekaran, Samantha Dias, Lily Coleman-Evans, William R Foster, Jon A Harper, Alex D Herbert, Catherine Tighe, Tristan Reuillon, Ryan West, Oliver Busby, Kamila Burdova, Damien Crepin, Sergi Ortoll, Kulthida Vaeteewoottacharn, Donniphat Dejsuphong, John Spencer, Hitesh Patel, Darren Le Grand, Thomas A Hunt, David M Andrews, Hiroyuki Yamano, Pedro R Cutillas, Antony W Oliver, Simon E Ward, Helfrid Hochegger.
      The Greatwall kinase inhibits PP2A-B55 phosphatase activity during mitosis to stabilise critical Cdk1-driven mitotic phosphorylation. Although Greatwall represents a potential oncogene and prospective therapeutic target, our understanding of the cellular and molecular consequences of chemical Greatwall inactivation remains limited. To address this, we introduce C-604, a highly selective Greatwall inhibitor, and characterise both immediate and long-term cellular responses to the chemical attenuation of Greatwall activity. We demonstrate that Greatwall inhibition causes systemic destabilisation of the mitotic phosphoproteome, premature mitotic exit and pleiotropic cellular pathologies. Importantly, we show that the cellular and molecular abnormalities associated with reduced Greatwall activity are specifically dependent on the B55α isoform, rather than other B55 variants, underscoring PP2A-B55α phosphatases as key mediators of the cytotoxic effects of Greatwall-targeting agents in human cells. Additionally, we establish that sensitivity to Greatwall inhibition varies in different cell line models and that dependency on Greatwall activity reflects the balance between Greatwall and B55α expression levels. Our findings highlight Greatwall dependency as a cell-specific vulnerability and propose the B55α-to-Greatwall expression ratio as a predictive biomarker of cellular responses to Greatwall-targeted therapeutics.
    DOI:  https://doi.org/10.1038/s41467-025-62943-z
  13. Biomolecules. 2025 Aug 21. pii: 1202. [Epub ahead of print]15(8):
    Histone H3 N-Terminal Tail Residues Important for Meiosis in Saccharomyces cerevisiae.
    Amy Prichard, Marnie Johansson, David T Kirkpatrick, Duncan J Clarke.
      Histone tail phosphorylation has diverse effects on a myriad of cellular processes, including cell division, and is highly conserved throughout eukaryotes. Histone H3 phosphorylation at threonine 3 (H3T3) during mitosis occurs at the inner centromeres and is required for proper biorientation of chromosomes on the mitotic spindle. While H3T3 is also phosphorylated during meiosis, a possible role for this modification has not been tested. Here, we asked if H3T3 phosphorylation is important for meiotic division by quantifying sporulation efficiency and spore viability in Saccharomyces cerevisiae mutants with a T3A amino acid substitution. The T3A substitution resulted in reduced sporulation efficiency and reduced spore viability. Analysis of two other H3 tail mutants, K4A and S10A, revealed different effects on sporulation efficiency and spore viability compared to the T3A mutant, suggesting that these phenotypes may be due to failures in distinct functions. To determine if the spindle checkpoint promotes spore viability of the T3A mutant, the MAD2 gene was deleted. This resulted in a severe reduction in spore viability following meiosis. Altogether, the data reveal an important function for histone H3 threonine 3 that requires monitoring by the spindle checkpoint to ensure successful completion of meiosis.
    Keywords:  H3T3; histone H3; histone modifications; meiosis; phosphorylation; sporulation
    DOI:  https://doi.org/10.3390/biom15081202
  14. Front Cell Dev Biol. 2025 ;13 1635110
    MRE11 orchestrates porcine oocyte meiotic progression by modulating the spindle assembly checkpoint.
    Dandan Zhang, Zaishan Yang, Yongteng Zhang, Fugui Fang, Hongguo Cao, Yunsheng Li, Zubing Cao, Yanfeng Xue, Mianqun Zhang.
       Introduction: Mre11 is a multisubunit nuclease involved in DNA repair, and its dysfunction often causes DNA damage sensitivity, genomic instability, telomere shortening, and aberrant meiosis. However, the specific roles of Mre11 in porcine oocyte meiosis remain unclear.
    Methods: In this study, porcine oocytes were treated with the Mre11-specific inhibitor mirin to investigate the function of Mre11 during meiotic maturation. Meiotic progression, spindle and chromosome structure, spindle migration, cytoplasmic actin polymerization, and DNA damage levels were assessed using immunofluorescence and relevant molecular markers including BubR1 and γH2A.X.
    Results: Inhibition of Mre11 activity led to failure of first polar body extrusion, with sustained BubR1 presence at kinetochores, indicating activation of the spindle assembly checkpoint (SAC). Mre11-inhibited oocytes showed disrupted spindle and chromosome organization due to decreased microtubule stability. Additionally, spindle migration to the oocyte cortex was impaired, correlating with reduced cytoplasmic actin polymerization. Elevated DNA damage levels were observed in treated oocytes as evidenced by increased γH2A.X staining.
    Discussion: These findings demonstrate that Mre11 is essential for porcine oocyte meiotic progression by maintaining normal spindle assembly, actin cytoskeleton dynamics, and SAC activity. DNA damage accumulation following Mre11 inhibition likely contributes to meiotic failure, highlighting its critical role in ensuring oocyte quality.
    Keywords:  MRE11; SAC; actin; oocytes development; spindle
    DOI:  https://doi.org/10.3389/fcell.2025.1635110
  15. Commun Biol. 2025 Aug 22. 8(1): 1262
    Maspin/SerpinB5 is a cytoskeleton-binding protein that regulates epithelial cell shape.
    Luiz E da Silva, Lia M G Paim, Tatiana Lyalina, Ana P J Menezes, Julia P C da Cunha, Susanne Bechstedt, Nathalie Cella.
      Maspin/SerpinB5 is an abundant and pleiotropic protein mostly expressed by epithelia. Initially described as a tumor suppressor, it has been reported as a regulator of cell adhesion, migration, and invasion. How intracellular Maspin orchestrates these processes is poorly understood. In this study, we utilized Affinity purification-Mass spectrometry (AP/MS) alongside in vitro reconstitution assays to establish that Maspin directly interacts with microtubules and microfilaments. Additionally, CRISPR/Cas9-mediated GFP tagging of endogenous Maspin, combined with immunostaining, revealed its localization at the cortical cytoskeleton and the mitotic spindle. Depletion of Maspin by RNAi and CRISPR/Cas9 in non-transformed epithelial cell lines modifies cell-cell contact and promotes cytoskeletal rearrangements. Concomitantly, we observed a modest upregulation of mesenchymal markers during interphase and abnormal cell rounding during mitosis. An evaluation of Maspin's effect on microtubules revealed that it suppresses their growth in vitro and in cells. Collectively, these results demonstrate that Maspin acts dynamically at the interface of the cytoskeleton and adhesion sites, modulating cell shape.
    DOI:  https://doi.org/10.1038/s42003-025-08688-3
  16. Research (Wash D C). 2025 ;8 0812
    Decoding Mitotic Chromosome Assembly: Three Rules Governing Condensin-Cohesin Engagement.
    Haiyan Yan, Xinyu Zhou, Fangwei Wang.
      Mitotic chromosome formation depends on coordinated SMC complex activities, yet how condensin engages cohesin during this process remains unclear. Samejima et al. combined synchronized mitotic entry, auxin-inducible degrons, high-resolution Hi-C, live-cell imaging, quantitative proteomics, and polymer simulations to dissect condensin I, condensin II, and cohesin interplay in vertebrate cells. They showed that condensins actively displace extrusive cohesin to dismantle interphase chromatin and build nested mitotic loops. Condensin II generates large, helical loops, and condensin I forms finer loops, together yielding the canonical rodlike mitotic chromosome. Cohesin, while preserving sister-chromatid cohesion, relocates to loop tips without blocking condensin. The study also reports the first in vivo measurements of condensin loop-extrusion speed. This work establishes a mechanistic, quantitative framework for mitotic chromosome architecture and offers predictive models for future genome-organization- and SMC-related pathology studies.
    DOI:  https://doi.org/10.34133/research.0812
  17. Mol Biol Cell. 2025 Aug 20. mbcE24120577
    Dynamic remodeling of centrioles and the microtubule cytoskeleton in the lifecycle of chytrid fungi.
    Alexandra F Long, Krishnakumar Vasudevan, Andrew Swafford, Claire M Venard, Jason E Stajich, Lillian K Fritz-Laylin, Jessica L Feldman, Tim Stearns.
      Cell movement and division are complex behaviors driven by a dynamic internal cytoskeleton. The molecular components and principles of cytoskeletal assembly are well studied, but less is known about cytoskeletal remodeling events, including how centrioles transition from ciliary base to centrosome. Here we address this using the chytrid Rhizoclosmatium globosum, a zoosporic fungus which has centrioles and cilia, lost in most fungal lineages. Chytrids undergo reorganization of their microtubule cytoskeleton as they grow from zoospore to multinucleated coenocyte. We use evolutionary comparison, RNA sequencing, and expansion microscopy to understand this reorganization and further develop this organism as a model for evolutionary cell biology. We find that when motile zoospores transition to sessile sporangia, cilia are retracted into the cytoplasm and degraded, while centrioles detach from the ciliary axoneme yet persist. During the mitotic cycles, short centrioles are associated with a centrosome-like microtubule-organizing center (MTOC) and a dense microtubule array at the spindle pole. After the mitotic cycles, centrioles elongate and form cilia, driven by transcription of genes associated with centriole maturation and ciliogenesis, and microtubule bundles are reorganized. Thus, in chytrids structural remodeling of the centriole is temporally coupled to specific changes in cytoskeletal organization over the coenocytic life cycle.
    DOI:  https://doi.org/10.1091/mbc.E24-12-0577
  18. Nat Commun. 2025 Aug 27. 16(1): 8008
    Upstream open reading frame translation enhances immunogenic peptide presentation in mitotically arrested cancer cells.
    Alexander Kowar, Jonas P Becker, Rossella Del Pizzo, Zhiwei Tang, Julien Champagne, Kathrin Wellach, Kiana Samimi, Ariel Galindo-Albarrán, Pierre-René Körner, Jasmine Montenegro Navarro, Andrés Elía, Fiona Megan Tilghman, Hanan Sakeer, Marco Antonio Mendoza-Parra, Angelika B Riemer, Reuven Agami, Fabricio Loayza-Puch.
      Mitosis is a critical phase of the cell cycle and a vulnerable point where cancer cells can be disrupted, causing cell death and inhibiting tumor growth. Challenges such as drug resistance persist in clinical applications. During mitosis, mRNA translation is generally downregulated, while non-canonical translation of specific transcripts continues. Here, we show that mitotic cancer cells redistribute ribosomes toward the 5' untranslated region (5' UTR) and beginning of the coding sequence (CDS), enhancing translation of thousands of upstream open reading frames (uORFs) and upstream overlapping open reading frames (uoORFs). This mitotic induction of uORF/uoORF enriches human leukocyte antigen (HLA) presentation of non-canonical peptides on the surface of cancer cells after mitotic inhibitor treatment. Functional assays indicate these epitopes provoke cancer-cell killing by T cells. Our findings highlight the therapeutic potential of targeting uORF/uoORF-derived epitopes with mitotic inhibitors to enhance immune recognition and tumor cell elimination.
    DOI:  https://doi.org/10.1038/s41467-025-63405-2
  19. Ann Med Surg (Lond). 2025 Jul;87(7): 4165-4172
    PLK1 inhibitors for the treatment of colorectal cancer.
    Peng Ye, Zhen Zhang, Dingyue Zhang, Mingyue Zhang, Mengping Wang, Peiling Cai, Ying Huang, Yongyan Song.
      Polo-like kinase 1 (PLK1) is a key regulator in mitosis and a highly potent target for anti-cancer therapies. Several PLK1 inhibitors have been developed and evaluated for cancer treatment. However, none of them has yet been approved for clinical usage, mostly due to their low response rates in cancer patients. A recent phase I trial reported a 44% partial response rate of onvansertib, a PLK1 inhibitor, in the treatment of patients with KRAS-mutated metastatic colorectal cancer, indicating that PLK1 inhibitor might be suitable for the treatment of this specific subtype of cancer. This review summarizes the results of preclinical experiments and clinical trials of PLK1 inhibitors, with colorectal cancer as a focus, in hope of facilitating future investigations in this research field.
    Keywords:  PLK1 inhibitor; anti-tumor therapy; colorectal cancer
    DOI:  https://doi.org/10.1097/MS9.0000000000003373
  20. Methods Mol Biol. 2025 ;2958 71-81
    Fast Super-Resolution Live Cell Imaging of Nuclear Membrane-Endoplasmic Reticulum Dynamics.
    Swapnil Sahoo, Abdur Rahaman.
      The nuclear membrane undergoes continuous remodelling during the life cycle of all eukaryotic cells. The endoplasmic reticulum remains continuous with the nuclear membrane and regulates this nuclear remodelling process. Here in this chapter, we describe in detail a protocol for high-speed imaging of nuclear membrane/endoplasmic reticulum dynamic structure in live cell using fluorescent endoplasmic reticulum resident marker (GFP-KDEL). We used super-resolution microscope to capture this dynamic event. This protocol will help visualize the dynamic changes in nuclear membrane/endoplasmic reticulum structure at different cell cycle stages and understand the role of various cellular factors in this process.
    Keywords:  Endoplasmic reticulum; High-speed imaging; Live cell imaging; Nuclear membrane; Super-resolution
    DOI:  https://doi.org/10.1007/978-1-0716-4714-1_5
  21. Nat Commun. 2025 Aug 25. 16(1): 7929
    Epsin1 enforces a condensation-dependent checkpoint for ubiquitylated cargo during clathrin-mediated endocytosis.
    Susovan Sarkar, Hao-Yang Liu, Feng Yuan, Brandon T Malady, Liping Wang, Eileen M Lafer, Jessica Perez, Jon M Huibregtse, Jeanne C Stachowiak.
      Clathrin-mediated endocytosis internalizes proteins and lipids from the cell surface. A flexible condensate of initiator proteins catalyzes assembly of clathrin-coated vesicles in diverse organisms. Here we reveal that an endocytic adaptor protein, Epsin1, conditionally stabilizes this network, creating a cargo-dependent endocytic checkpoint. Epsin1 recruits ubiquitylated cargo to endocytic sites. Using in vitro assays, we demonstrate that Epsin1 destabilizes condensation of initiator proteins in the absence of ubiquitin. However, when polyubiquitin is present, Epsin1 binds to both ubiquitin and initiator proteins, stabilizing condensation. Similarly, in mammalian cells, endocytosis is disrupted by removal of either ubiquitin or Epsin1. When both components are removed simultaneously, endocytic defects are largely rescued, although the ability to preferentially internalize ubiquitylated cargo is lost. These results suggest that Epsin1 tunes protein condensation to internalize ubiquitylated cargo. More broadly, these findings illustrate how a balance of attractive and repulsive molecular interactions can exert dynamic control over cellular events.
    DOI:  https://doi.org/10.1038/s41467-025-63238-z
  22. Semin Cell Dev Biol. 2025 Aug 23. pii: S1084-9521(25)00053-9. [Epub ahead of print]175 103643
    Mechanistic modeling of mitosis: Insights from three collaborative case studies.
    Jing Chen, Daniela Cimini.
      Mechanistic mathematical modeling has become an essential tool in modern biological research due to its powerful ability to integrate diverse data, generate hypotheses, and guide experimental design. It is particularly valuable for studying complex cellular mechanisms involving numerous interacting components. While the full dynamics of such systems usually elude direct experimental observation, modeling provides a means to integrate fragmented data with reasonable and/or informed assumptions into coherent mechanistic frameworks, simulate system behavior, and identify promising directions for further experimentation. When closely integrated with experiments, modeling can greatly accelerate progress in cell biology. However, the value of modeling is not automatic-it must be earned through careful model construction, critical interpretation of results, and thoughtful design of follow-up experiments. To demystify this process, we review three of our collaborative projects in mitosis, drawing on our experiences as a modeler and an experimentalist. We describe how the projects were initiated, why specific modeling approaches were chosen, how models were developed and refined, how model predictions guided new experiments, and how integrated modeling and experimentation led to deeper mechanistic insights. Finally, we emphasize that at the heart of every successful collaboration lies human connection. Productive cross-disciplinary communication is fundamental to bridging experimental and modeling perspectives and fully realizing the potential of integrative approaches in modern cell biology.
    Keywords:  Biophysical modeling; Mathematical modeling; Mechanistic modeling; Mitosis; Spindle assembly
    DOI:  https://doi.org/10.1016/j.semcdb.2025.103643
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