7,356 results match your criteria spindle microtubules


Conjugated linoleic acid improves meiotic spindle morphology and developmental competence of heat-stressed bovine oocyte.

Theriogenology 2021 May 27;172:67-72. Epub 2021 May 27.

Pasargad Institute for Advanced Innovative Solutions (PIAIS), Khatam University, Tehran 1991633356, Iran.

This study was conducted to elucidate the effects of introducing conjugated linoleic acid (CLA) on meiotic spindle organization of heat stressed (HS) matured oocytes and the resulting blastocysts DNA methylation as well as the expression of the genes involved in DNA methylation (DNMT3a, DNMT3b and DNMT1). Immature bovine oocytes were cultured at 41 °C for the first 12 h and 38.5 °C for the second 12 h of maturation time in the presence of 0 and 50 μM of CLA (HS and HS + CLA groups, respectively). Read More

View Article and Full-Text PDF

Microtubule re-organization during female meiosis in .

Elife 2021 Jun 11;10. Epub 2021 Jun 11.

University of Virginia, Charlottesville, United States.

The female meiotic spindles of most animals are acentrosomal and undergo striking morphological changes while transitioning from metaphase to anaphase. The ultra-structure of acentrosomal spindles, and how changes to this structure correlate with such dramatic spindle rearrangements remains largely unknown. To address this, we applied light microscopy, large-scale electron tomography and mathematical modeling of female meiotic spindles undergoing the transition from metaphase to anaphase. Read More

View Article and Full-Text PDF

Semi-automatic stitching of filamentous structures in image stacks from serial-section electron tomography.

J Microsc 2021 Jun 10. Epub 2021 Jun 10.

Zuse Institute Berlin, Takustraße 7, Berlin, 14195, Germany.

We present a software-assisted workflow for the alignment and matching of filamentous structures across a three-dimensional (3D) stack of serial images. This is achieved by combining automatic methods, visual validation, and interactive correction. After the computation of an initial automatic matching, the user can continuously improve the result by interactively correcting landmarks or matches of filaments. Read More

View Article and Full-Text PDF

Mitotic poleward flux: Finding balance between microtubule dynamics and sliding.

Bioessays 2021 Jun 4:e2100079. Epub 2021 Jun 4.

Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), Copenhagen, Denmark.

Continuous poleward motion of microtubules in metazoan mitotic spindles has been fascinating generations of cell biologists over the last several decades. In human cells, this so-called poleward flux was recently shown to be driven by the coordinated action of four mitotic kinesins. The sliding activities of kinesin-5/EG5 and kinesin-12/KIF15 are sequentially supported by kinesin-7/CENP-E at kinetochores and kinesin-4/KIF4A on chromosome arms, with the individual contributions peaking during prometaphase and metaphase, respectively. Read More

View Article and Full-Text PDF

Differential regulation of single microtubules and bundles by a three-protein module.

Nat Chem Biol 2021 Jun 3. Epub 2021 Jun 3.

Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.

A remarkable feature of the microtubule cytoskeleton is the coexistence of subpopulations having different dynamic properties. A prominent example is the anaphase spindle, where stable antiparallel bundles exist alongside dynamic microtubules and provide spatial cues for cytokinesis. How are the dynamics of spatially proximal arrays differentially regulated? We reconstitute a minimal system of three midzone proteins: microtubule-crosslinker PRC1 and its interactors CLASP1 and Kif4A, proteins that promote and suppress microtubule elongation, respectively. Read More

View Article and Full-Text PDF

Ctf3/CENP-I provides a docking site for the desumoylase Ulp2 at the kinetochore.

J Cell Biol 2021 Aug 3;220(8). Epub 2021 Jun 3.

Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA.

The step-by-step process of chromosome segregation defines the stages of the cell cycle. In eukaryotes, signals controlling these steps converge upon the kinetochore, a multiprotein assembly that connects spindle microtubules to chromosomal centromeres. Kinetochores control and adapt to major chromosomal transactions, including replication of centromeric DNA, biorientation of sister centromeres on the metaphase spindle, and transit of sister chromatids into daughter cells during anaphase. Read More

View Article and Full-Text PDF

Kinetoplastid kinetochore proteins KKT2 and KKT3 have unique centromere localization domains.

J Cell Biol 2021 Aug 3;220(8). Epub 2021 Jun 3.

Department of Biochemistry, University of Oxford, Oxford, UK.

The kinetochore is the macromolecular protein complex that assembles onto centromeric DNA and binds spindle microtubules. Evolutionarily divergent kinetoplastids have an unconventional set of kinetochore proteins. It remains unknown how kinetochores assemble at centromeres in these organisms. Read More

View Article and Full-Text PDF

Kinesin-6 Klp9 orchestrates spindle elongation by regulating microtubule sliding and growth.

Elife 2021 Jun 3;10. Epub 2021 Jun 3.

UMR144, Institut Curie, Paris, France.

Mitotic spindle function depends on the precise regulation of microtubule dynamics and microtubule sliding. Throughout mitosis, both processes have to be orchestrated to establish and maintain spindle stability. We show that during anaphase B spindle elongation in , the sliding motor Klp9 (kinesin-6) also promotes microtubule growth , Klp9 can enhance and dampen microtubule growth, depending on the tubulin concentration. Read More

View Article and Full-Text PDF

Vanadocene dichloride induces apoptosis in HeLa cells through depolymerization of microtubules and inhibition of Eg5.

J Biol Inorg Chem 2021 May 31. Epub 2021 May 31.

School of Biotechnology, National Institute of Technology Calicut, Calicut, Kerala, 673601, India.

Vanadocene dichloride (VDC), a vanadium containing metallocene dihalide exhibits promising anticancer activity. However, its mechanism of action remains elusive as several diverse targets and pathways have been proposed for its anticancer activity. In this study, we observed that VDC inhibited the proliferation of mammalian cancer cells and induced apoptotic cell death by altering the mitochondrial membrane potential and the expression of bcl2 and bax. Read More

View Article and Full-Text PDF

The metaphase spindle at steady state - Mechanism and functions of microtubule poleward flux.

Semin Cell Dev Biol 2021 May 27. Epub 2021 May 27.

Cell Division and Cytoskeleton, Danish Cancer Society Research Center (DCRC), Strandboulevarden 49, 2100 Copenhagen, Denmark.

The mitotic spindle is a bipolar cellular structure, built from tubulin polymers, called microtubules, and interacting proteins. This macromolecular machine orchestrates chromosome segregation, thereby ensuring accurate distribution of genetic material into the two daughter cells during cell division. Powered by GTP hydrolysis upon tubulin polymerization, the microtubule ends exhibit a metastable behavior known as the dynamic instability, during which they stochastically switch between the growth and shrinkage phases. Read More

View Article and Full-Text PDF

Measuring force generation within reconstituted microtubule bundle assemblies using optical tweezers.

Cytoskeleton (Hoboken) 2021 May 29. Epub 2021 May 29.

Department of Chemical Engineering, University of Mississippi, University, Mississippi, USA.

Kinesins and microtubule associated proteins (MAPs) are critical to sustain life, facilitating cargo transport, cell division, and motility. To interrogate the mechanistic underpinnings of their function, these microtubule-based motors and proteins have been studied extensively at the single molecule level. However, a long-standing issue in the single molecule biophysics field has been how to investigate motors and associated proteins within a physiologically relevant environment in vitro. Read More

View Article and Full-Text PDF

The multifunctional spindle midzone in vertebrate cells at a glance.

J Cell Sci 2021 May 27;134(10). Epub 2021 May 27.

Department of Biology, Morrill Science Center, University of Massachusetts, 611 N. Pleasant Street, Amherst 01003, USA.

During anaphase, a microtubule-containing structure called the midzone forms between the segregating chromosomes. The midzone is composed of an antiparallel array of microtubules and numerous microtubule-associated proteins that contribute to midzone formation and function. In many cells, the midzone is an important source of signals that specify the location of contractile ring assembly and constriction. Read More

View Article and Full-Text PDF

Confinement size determines the architecture of Ran-induced microtubule networks.

Soft Matter 2021 May 27. Epub 2021 May 27.

Department of Molecular Biology, Princeton University, Princeton, NJ, USA.

The organization of microtubules (MTs) is critical for cells during interphase and mitosis. During mitotic spindle assembly, MTs are made and organized around chromosomes in a process regulated by RanGTP. The role of RanGTP has been explored in Xenopus egg extracts, which are not limited by a cell membrane. Read More

View Article and Full-Text PDF

Spastin interacts with CRMP5 to promote spindle organization in mouse oocytes by severing microtubules.

Zygote 2021 May 26:1-12. Epub 2021 May 26.

Department of Gynaecology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang310014, China.

Microtubule-severing protein (MTSP) is critical for the survival of both mitotic and postmitotic cells. However, the study of MTSP during meiosis of mammalian oocytes has not been reported. We found that spastin, a member of the MTSP family, was highly expressed in oocytes and aggregated in spindle microtubules. Read More

View Article and Full-Text PDF

Biomechanics of chromosome alignment at the spindle midplane.

Curr Biol 2021 May;31(10):R574-R585

Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54, 10000 Zagreb, Croatia. Electronic address:

During metaphase, chromosomes are aligned in a lineup at the equatorial plane of the spindle to ensure synchronous poleward movement of chromatids in anaphase and proper nuclear reformation at the end of mitosis. Chromosome alignment relies on microtubules, several types of motor protein and numerous other microtubule-associated and regulatory proteins. Because of the multitude of players involved, the mechanisms of chromosome alignment are still under debate. Read More

View Article and Full-Text PDF

Unraveling pathologies underlying chromosomal instability in cancers.

Cancer Sci 2021 May 25. Epub 2021 May 25.

Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo, Japan.

Aneuploidy is a widespread feature of malignant tumors that arises through persistent chromosome mis-segregation in mitosis associated with a pathological condition called chromosomal instability, or CIN. Since CIN is known to have a causal relationship with poor prognosis accompanying by multi-drug resistance, tumor relapse, and metastasis, many research groups have endeavored to understand the mechanisms underlying CIN. In this review, we overview possible etiologies of CIN. Read More

View Article and Full-Text PDF

CENP-C functions in centromere assembly, the maintenance of CENP-A asymmetry and epigenetic age in Drosophila germline stem cells.

PLoS Genet 2021 May 20;17(5):e1009247. Epub 2021 May 20.

Centre for Chromosome Biology, Biomedical Sciences, National University of Ireland Galway, Galway, Ireland.

Germline stem cells divide asymmetrically to produce one new daughter stem cell and one daughter cell that will subsequently undergo meiosis and differentiate to generate the mature gamete. The silent sister hypothesis proposes that in asymmetric divisions, the selective inheritance of sister chromatids carrying specific epigenetic marks between stem and daughter cells impacts cell fate. To facilitate this selective inheritance, the hypothesis specifically proposes that the centromeric region of each sister chromatid is distinct. Read More

View Article and Full-Text PDF

Neuronal SETD2 activity links microtubule methylation to an anxiety-like phenotype in mice.

Brain 2021 May 20. Epub 2021 May 20.

Center for Precision Environmental Health, Baylor College of Medicine, Houston, TX, 77030, USA.

Gene discovery efforts in autism spectrum disorder have identified heterozygous defects in chromatin remodeler genes, the" readers, writers and erasers" of methyl marks on chromatin, as major contributors to this disease. Despite this advance, a convergent etiology between these defects and aberrant chromatin architecture or gene expression has remained elusive. Recently, data have begun to emerge that chromatin remodelers also function directly on the cytoskeleton. Read More

View Article and Full-Text PDF

The Trypanosoma brucei subpellicular microtubule array is organized into functionally discrete subdomains defined by microtubule associated proteins.

PLoS Pathog 2021 May 19;17(5):e1009588. Epub 2021 May 19.

Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, United States of America.

Microtubules are inherently dynamic cytoskeletal polymers whose length and organization can be altered to perform essential functions in eukaryotic cells, such as providing tracks for intracellular trafficking and forming the mitotic spindle. Microtubules can be bundled to create more stable structures that collectively propagate force, such as in the flagellar axoneme, which provides motility. The subpellicular microtubule array of the protist parasite Trypanosoma brucei, the causative agent of African sleeping sickness, is a remarkable example of a highly specialized microtubule bundle. Read More

View Article and Full-Text PDF

Mitotic checkpoint regulator RAE1 promotes tumor growth in colorectal cancer.

Cancer Sci 2021 May 18. Epub 2021 May 18.

Department of Surgery, Kyushu University Beppu Hospital, Oita, Japan.

Microtubules are among the most successful targets for anticancer therapy because they play important roles in cell proliferation as they constitute the mitotic spindle, which is critical for chromosome segregation during mitosis. Hence, identifying new therapeutic targets encoding proteins that regulate microtubule assembly and function specifically in cancer cells is critical. In the present study, we identified a candidate gene that promotes tumor progression, ribonucleic acid export 1 (RAE1), a mitotic checkpoint regulator, on chromosome 20q through a bioinformatics approach using datasets of colorectal cancer (CRC) including The Cancer Genome Atlas (TCGA). Read More

View Article and Full-Text PDF

Repurposing of synaptonemal complex proteins for kinetochores in Kinetoplastida.

Open Biol 2021 May 19;11(5):210049. Epub 2021 May 19.

Department of Biochemistry, University of Oxford, Oxford, UK.

Chromosome segregation in eukaryotes is driven by the kinetochore, a macromolecular complex that connects centromeric DNA to microtubules of the spindle apparatus. Kinetochores in well-studied model eukaryotes consist of a core set of proteins that are broadly conserved among distant eukaryotic phyla. By contrast, unicellular flagellates of the class Kinetoplastida have a unique set of 36 kinetochore components. Read More

View Article and Full-Text PDF

Inter-organelle interactions between the ER and mitotic spindle facilitates Zika protease cleavage of human Kinesin-5 and results in mitotic defects.

iScience 2021 May 31;24(5):102385. Epub 2021 Mar 31.

Department of Biochemistry and Molecular Biology, LSU School of Medicine & Health Sciences Center, New Orleans, LA 70112, USA.

Here we identify human Kinesin-5, Kif11/HsEg5, as a cellular target of Zika protease. We show that Zika NS2B-NS3 protease targets several sites within the motor domain of HsEg5 irrespective of motor binding to microtubules. The native integral ER-membrane protease triggers mitotic spindle positioning defects and a prolonged metaphase delay in cultured cells. Read More

View Article and Full-Text PDF

AtNUF2 modulates spindle microtubule organization and chromosome segregation during mitosis.

Plant J 2021 May 16. Epub 2021 May 16.

State Key Laboratory of Hybrid Rice, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

The NDC80 complex is a conserved eukaryotic complex composed of four subunits (NUF2, SPC25, NDC80, and SPC24). In yeast and animal cells, the complex is located at the outer layer of the kinetochore, connecting the inner layer of the kinetochore and spindle microtubules (MTs) during cell division. In higher plants, the relationship of the NDC80 complex with MTs is still unclear. Read More

View Article and Full-Text PDF

TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity.

J Cell Biol 2021 Jul 13;220(7). Epub 2021 May 13.

Laboratory of Protein Dynamics and Signaling, National Institutes of Health, National Cancer Institute, Center for Cancer Research, Frederick, MD.

Centrosomes are composed of a centriolar core surrounded by pericentriolar material that nucleates microtubules. The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. We show that TRIM37 does not control centriole duplication, structure, or the ability of centrioles to form cilia but instead prevents assembly of an ectopic centrobin-scaffolded structured condensate that forms by budding off of centrosomes. Read More

View Article and Full-Text PDF

Targeting the actin/tropomyosin cytoskeleton in epithelial ovarian cancer reveals multiple mechanisms of synergy with anti-microtubule agents.

Br J Cancer 2021 May 12. Epub 2021 May 12.

School of Medical Sciences, Faculty of Medicine, University of NSW Sydney, Sydney, NSW, Australia.

Background: Anti-microtubule agents are widely used to treat ovarian cancers, but the efficacy is often compromised by drug resistance. We investigated co-targeting the actin/tropomyosin cytoskeleton and microtubules to increase treatment efficacy in ovarian cancers and potentially overcome resistance.

Methods: The presence of tropomyosin-3. Read More

View Article and Full-Text PDF

Expression Patterns and Levels of All Tubulin Isotypes Analyzed in GFP Knock-In C. elegans Strains.

Cell Struct Funct 2021 May 8. Epub 2021 May 8.

Laboratory of Developmental Dynamics, Graduate School of Life Sciences, Tohoku University.

Most organisms have multiple α- and β-tubulin isotypes that likely contribute to the diversity of microtubule (MT) functions. To understand the functional differences of tubulin isotypes in Caenorhabditis elegans, which has nine α-tubulin isotypes and six β-tubulin isotypes, we systematically constructed null mutants and GFP-fusion strains for all tubulin isotypes with the CRISPR/Cas9 system and analyzed their expression patterns and levels in adult hermaphrodites. Four isotypes-α-tubulins TBA-1 and TBA-2 and β-tubulins TBB-1 and TBB-2-were expressed in virtually all tissues, with a distinct tissue-specific spectrum. Read More

View Article and Full-Text PDF

Parental genome unification is highly error-prone in mammalian embryos.

Cell 2021 May 7;184(11):2860-2877.e22. Epub 2021 May 7.

Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany. Electronic address:

Most human embryos are aneuploid. Aneuploidy frequently arises during the early mitotic divisions of the embryo, but its origin remains elusive. Human zygotes that cluster their nucleoli at the pronuclear interface are thought to be more likely to develop into healthy euploid embryos. Read More

View Article and Full-Text PDF

Structure and Mechanics of Dynein Motors.

Annu Rev Biophys 2021 05;50:549-574

Biophysics Graduate Group, University of California, Berkeley, California 94720, USA; email:

Dyneins make up a family of AAA+ motors that move toward the minus end of microtubules. Cytoplasmic dynein is responsible for transporting intracellular cargos in interphase cells and mediating spindle assembly and chromosome positioning during cell division. Other dynein isoforms transport cargos in cilia and power ciliary beating. Read More

View Article and Full-Text PDF

The Putative RNA-Binding Protein Dri1 Promotes the Loading of Kinesin-14/Klp2 to the Mitotic Spindle and Is Sequestered into Heat-Induced Protein Aggregates in Fission Yeast.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Laboratory of Molecular and Chemical Cell Biology, Graduate School of Integrated Sciences for Life, Hiroshima University, 1-3-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-8530, Japan.

Cells form a bipolar spindle during mitosis to ensure accurate chromosome segregation. Proper spindle architecture is established by a set of kinesin motors and microtubule-associated proteins. In most eukaryotes, kinesin-5 motors are essential for this process, and genetic or chemical inhibition of their activity leads to the emergence of monopolar spindles and cell death. Read More

View Article and Full-Text PDF

Structural characterization of KKT4, an unconventional microtubule-binding kinetochore protein.

Structure 2021 Apr 26. Epub 2021 Apr 26.

Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK. Electronic address:

The kinetochore is the macromolecular machinery that drives chromosome segregation by interacting with spindle microtubules. Kinetoplastids (such as Trypanosoma brucei), a group of evolutionarily divergent eukaryotes, have a unique set of kinetochore proteins that lack any significant homology to canonical kinetochore components. To date, KKT4 is the only kinetoplastid kinetochore protein that is known to bind microtubules. Read More

View Article and Full-Text PDF