6,448 results match your criteria mechanism microtubules

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

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

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

Simultaneous Targeting Tumor Cells and Cancer-Associated Fibroblasts with a Paclitaxel-Hyaluronan Bioconjugate: In Vitro Evaluation in Non-Melanoma Skin Cancer.

Biomedicines 2021 May 24;9(6). Epub 2021 May 24.

Laboratory of Cutaneous Physiopathology and Integrated Center of Metabolomics Research, San Gallicano Dermatologic Institute, IRCCS, 00144 Rome, Italy.

Background: Cancer-associated fibroblasts (CAFs) facilitate many aspects of cancer development by providing a structural framework rich in bioactive compounds. There are emerging studies proposing a combination of conventional anti-cancer therapies directed against neoplastic cells to molecules targeting tumor microenvironments.

Methods: The study evaluated the pharmacological properties of the anti-tumor agent paclitaxel conjugated to hyaluronic acid (HA) regarding non-melanoma skin cancer (NMSC) and the surrounding fibroblasts. Read More

View Article and Full-Text PDF

Microtubule Dynamics Plays a Vital Role in Plant Adaptation and Tolerance to Salt Stress.

Int J Mol Sci 2021 May 31;22(11). Epub 2021 May 31.

Institute of Agriculture & Life Science, Gyeongsang National University, Jinju 52828, Korea.

Although recent studies suggest that the plant cytoskeleton is associated with plant stress responses, such as salt, cold, and drought, the molecular mechanism underlying microtubule function in plant salt stress response remains unclear. We performed a comparative proteomic analysis between control suspension-cultured cells (A0) and salt-adapted cells (A120) established from root callus to investigate plant adaptation mechanisms to long-term salt stress. We identified 50 differentially expressed proteins (45 up- and 5 down-regulated proteins) in A120 cells compared with A0 cells. Read More

View Article and Full-Text PDF

Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy.

Biomedicines 2021 May 2;9(5). Epub 2021 May 2.

Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama 700-8530, Japan.

Paclitaxel (PTX) is a chemotherapeutical agent commonly used to treat several kinds of cancer. PTX is known as a microtubule-targeting agent with a primary molecular mechanism that disrupts the dynamics of microtubules and induces mitotic arrest and cell death. Simultaneously, other mechanisms have been evaluated in many studies. Read More

View Article and Full-Text PDF

Monopolar flocking of microtubules in collective motion.

Biochem Biophys Res Commun 2021 Jul 29;563:73-78. Epub 2021 May 29.

Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo, 060-0810, Hokkaido, Japan; Faculty of Science, Hokkaido University, Sapporo, 060-0810, Hokkaido, Japan. Electronic address:

Flocking is a fascinating coordinated behavior of living organisms or self-propelled particles (SPPs). Particularly, monopolar flocking has been attractive due to its potential applications in various fields. However, the underlying mechanism behind flocking and emergence of monopolar motion in flocking of SPPs has remained obscured. 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

Autoinhibition of Cnn binding to γ-TuRCs prevents ectopic microtubule nucleation and cell division defects.

J Cell Biol 2021 Aug 27;220(8). Epub 2021 May 27.

Department of Zoology, University of Cambridge, Cambridge, UK.

γ-Tubulin ring complexes (γ-TuRCs) nucleate microtubules. They are recruited to centrosomes in dividing cells via binding to N-terminal CM1 domains within γ-TuRC-tethering proteins, including Drosophila Centrosomin (Cnn). Binding promotes microtubule nucleation and is restricted to centrosomes in dividing cells, but the mechanism regulating binding remains unknown. Read More

View Article and Full-Text PDF

MARK4 controls ischaemic heart failure through microtubule detyrosination.

Nature 2021 May 26. Epub 2021 May 26.

Department of Medicine, Cardiovascular Division, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Myocardial infarction is a major cause of premature death in adults. Compromised cardiac function after myocardial infarction leads to chronic heart failure with systemic health complications and a high mortality rate. Effective therapeutic strategies are needed to improve the recovery of cardiac function after myocardial infarction. Read More

View Article and Full-Text PDF

Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins.

Nat Commun 2021 05 24;12(1):3065. Epub 2021 May 24.

Department of Biochemistry and Molecular Biophysics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.

In living cells, microtubules (MTs) play pleiotropic roles, which require very different mechanical properties. Unlike the dynamic MTs found in the cytoplasm of metazoan cells, the specialized cortical MTs from Toxoplasma gondii, a prevalent human pathogen, are extraordinarily stable and resistant to detergent and cold treatments. Using single-particle cryo-EM, we determine their ex vivo structure and identify three proteins (TrxL1, TrxL2 and SPM1) as bona fide microtubule inner proteins (MIPs). Read More

View Article and Full-Text PDF

Ccdc103 promotes myeloid cell proliferation and migration independent of motile cilia.

Dis Model Mech 2021 May 24;14(5). Epub 2021 May 24.

Molecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.

The pathology of primary ciliary dyskinesia (PCD) is predominantly attributed to impairment of motile cilia. However, PCD patients also have perplexing functional defects in myeloid cells, which lack motile cilia. Here, we show that coiled-coil domain-containing protein 103 (CCDC103), one of the genes that, when mutated, is known to cause PCD, is required for the proliferation and directed migration of myeloid cells. 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

Fast photothermal spatial light modulation for quantitative phase imaging at the nanoscale.

Nat Commun 2021 05 19;12(1):2921. Epub 2021 May 19.

Institute of Photonics and Electronics of the Czech Academy of Sciences, Prague, 18251, Czech Republic.

Spatial light modulators have become an essential tool for advanced microscopy, enabling breakthroughs in 3D, phase, and super-resolution imaging. However, continuous spatial-light modulation that is capable of capturing sub-millisecond microscopic motion without diffraction artifacts and polarization dependence is challenging. Here we present a photothermal spatial light modulator (PT-SLM) enabling fast phase imaging for nanoscopic 3D reconstruction. Read More

View Article and Full-Text PDF

Effects of TiO-NPs pretreatment on UV-B stress tolerance in Arabidopsis thaliana.

Chemosphere 2021 May 11;281:130809. Epub 2021 May 11.

Shanxi Normal University, Linfen, Shanxi, 041004, People's Republic of China; Higher Education Key Laboratory of Plant Molecular and Environmental Stress Response (Shanxi Normal University) in Shanxi Province, Linfen, Shanxi, 041000, People's Republic of China. Electronic address:

As the ozone hole in the North and South poles continues to increase, the entire ecosystem will face an environmental crisis caused by enhanced UV-B radiation. Considering the function of TiO and the application of nanomaterials in agriculture, the effect of TiO-NPs on UV-B stress tolerance in Arabidopsis was investigated. The phenotype of plants was determined, and the expression patterns of antioxidant systems and related genes were analyzed. Read More

View Article and Full-Text PDF

p27 controls autophagic vesicle trafficking in glucose-deprived cells via the regulation of ATAT1-mediated microtubule acetylation.

Cell Death Dis 2021 May 13;12(5):481. Epub 2021 May 13.

MCD, Centre de Biologie Intégrative, Université de Toulouse, CNRS, UPS, 31062, Toulouse, Cedex, France.

The cyclin-dependent kinase inhibitor p27 (p27) has been involved in promoting autophagy and survival in conditions of metabolic stress. While the signaling cascade upstream of p27 leading to its cytoplasmic localization and autophagy induction has been extensively studied, how p27 stimulates the autophagic process remains unclear. Here, we investigated the mechanism by which p27 promotes autophagy upon glucose deprivation. 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

Cereblon regulates the proteotoxicity of tau by tuning the chaperone activity of DNAJA1.

J Neurosci 2021 May 7. Epub 2021 May 7.

Laboratory of Molecular Neurobiology

Protein aggregation can induce explicit neurotoxic events that trigger a number of presently untreatable neurodegenerative disorders. Chaperones, on the other hand, play a neuroprotective role due to their ability to unfold and refold abnormal proteins. Progressive nature of neurotoxic events makes it important to discover endogenous factors that affect pathological and molecular phenotypes of neurodegeneration in animal models. Read More

View Article and Full-Text PDF

Nuclear Lamin A/C Expression Is a Key Determinant of Paclitaxel Sensitivity.

Mol Cell Biol 2021 May 10. Epub 2021 May 10.

Sylvester Comprehensive Cancer Center, Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL 33136

Paclitaxel is a key member of the Taxane (Taxol/paclitaxel, docetaxel/taxotere) family of successful drugs used in the current treatment of several solid tumors, including ovarian cancer. The molecular target of Taxol/paclitaxel has been identified as tubulin, and paclitaxel binding alters the dynamics and thus stabilizes microtubule bundles. Traditionally, the anti-cancer mechanism of paclitaxel has been thought to originate from its interfering with the role of microtubules in mitosis, resulting in mitotic arrest and subsequent apoptosis. 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

Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment.

Int J Mol Sci 2021 Apr 16;22(8). Epub 2021 Apr 16.

Pediatric Oncology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica Sacro Cuore, 00168 Rome, Italy.

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Read More

View Article and Full-Text PDF

S6K1 Is Indispensible for Stress-Induced Microtubule Acetylation and Autophagic Flux.

Cells 2021 Apr 17;10(4). Epub 2021 Apr 17.

Department of Medical Biology and Genetics, Faculty of Biology, University of Gdańsk, Wita Stwosza 59, 80-308 Gdańsk, Poland.

Autophagy is a specific macromolecule and organelle degradation process. The target macromolecule or organelle is first enclosed in an autophagosome, and then delivered along acetylated microtubules to the lysosome. Autophagy is triggered by stress and largely contributes to cell survival. Read More

View Article and Full-Text PDF

Effect of ethanol and cocaine on [C]MPC-6827 uptake in SH-SY5Y cells.

Mol Biol Rep 2021 Apr 20;48(4):3871-3876. Epub 2021 Apr 20.

Department of Radiology, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.

Microtubules (MTs) are structural units in the cytoskeleton. In brain cells they are responsible for axonal transport, information processing, and signaling mechanisms. Proper function of these processes is critical for healthy brain functions. Read More

View Article and Full-Text PDF

A laminin-based local regulatory network in the testis that supports spermatogenesis.

Semin Cell Dev Biol 2021 Apr 17. Epub 2021 Apr 17.

The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China. Electronic address:

In adult rat testes, the basement membrane is structurally constituted by laminin and collagen chains that lay adjacent to the blood-testis barrier (BTB). It plays a crucial scaffolding role to support spermatogenesis. On the other hand, laminin-333 comprised of laminin-α3/ß3/γ3 at the apical ES (ectoplasmic specialization, a testis-specific cell-cell adherens junction at the Sertoli cell-step 8-19 spermatid interface) expressed by spermatids serves as a unique cell adhesion protein that forms an adhesion complex with α6ß1-integrin expressed by Sertoli cells to support spermiogenesis. Read More

View Article and Full-Text PDF

mTORC1/rpS6 and p-FAK-Y407 signaling regulate spermatogenesis: Insights from studies of the adjudin pharmaceutical/toxicant model.

Semin Cell Dev Biol 2021 Apr 15. Epub 2021 Apr 15.

The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Institute of Reproductive Medicine, Nantong University School of Medicine, Nantong, Jiangsu 226001, China; The Population Council, Center for Biomedical Research, 1230 York Ave, New York, NY 10065, United States. Electronic address:

In rodents and humans, the major cellular events at spermatogenesis include self-renewal of spermatogonial stem cells and undifferentiated spermatogonia via mitosis, commitment of spermatogonia to differentiation and transformation to spermatocytes, meiosis, spermiogenesis, and the release of spermatozoa at spermiation. While details of the morphological changes during these cellular events have been delineated, knowledge gap exists between the morphological changes in the seminiferous epithelium and the underlying molecular mechanism(s) that regulate these cellular events. Even though many of the regulatory proteins and biomolecules that modulate spermatogenesis are known based on studies using genetic models, the underlying regulatory mechanism(s), in particular signaling pathways/proteins, remain unexplored since much of the information regarding the signaling regulation is unknown. Read More

View Article and Full-Text PDF

Microtubule and tubulin binding and regulation of microtubule dynamics by the antibody drug conjugate (ADC) payload, monomethyl auristatin E (MMAE): Mechanistic insights into MMAE ADC peripheral neuropathy.

Toxicol Appl Pharmacol 2021 06 20;421:115534. Epub 2021 Apr 20.

Safety Assessment, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address:

Monomethyl auristatin E (MMAE) is a potent anti-cancer microtubule-targeting agent (MTA) used as a payload in three approved MMAE-containing antibody drug conjugates (ADCs) and multiple ADCs in clinical development to treat different types of cancers. Unfortunately, MMAE-ADCs can induce peripheral neuropathy, a frequent adverse event leading to treatment dose reduction or discontinuation and subsequent clinical termination of many MMAE-ADCs. MMAE-ADC-induced peripheral neuropathy is attributed to non-specific uptake of the ADC in peripheral nerves and release of MMAE, disrupting microtubules (MTs) and causing neurodegeneration. Read More

View Article and Full-Text PDF

Two modes of PRC1-mediated mechanical resistance to kinesin-driven microtubule network disruption.

Curr Biol 2021 Apr 6. Epub 2021 Apr 6.

Department of Biological Sciences, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY 12180, USA. Electronic address:

The proper organization of the microtubule-based spindle during cell division requires the collective activity of many different proteins. These include non-motor microtubule-associated proteins (MAPs), whose functions include crosslinking microtubules to regulate filament sliding rates and assemble microtubule arrays. One such protein is PRC1, an essential MAP that has been shown to preferentially crosslink overlapping antiparallel microtubules at the spindle midzone. Read More

View Article and Full-Text PDF

Colchicine acts selectively in the liver to induce hepatokines that inhibit myeloid cell activation.

Nat Metab 2021 04 12;3(4):513-522. Epub 2021 Apr 12.

Department of Systems Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.

Colchicine has served as a traditional medicine for millennia and remains widely used to treat inflammatory and other disorders. Colchicine binds tubulin and depolymerizes microtubules, but it remains unclear how this mechanism blocks myeloid cell recruitment to inflamed tissues. Here we show that colchicine inhibits myeloid cell activation via an indirect mechanism involving the release of hepatokines. Read More

View Article and Full-Text PDF

The E3 ligase MREL57 modulates microtubule stability and stomatal closure in response to ABA.

Nat Commun 2021 04 12;12(1):2181. Epub 2021 Apr 12.

State Key Laboratory of Plant Physiology and Biochemistry; Department of Plant Sciences, College of Biological Sciences, China Agricultural University, Beijing, China.

Regulation of stomatal movement is critical for plant adaptation to environmental stresses. The microtubule cytoskeleton undergoes disassembly, which is critical for stomatal closure in response to abscisic acid (ABA). However, the mechanism underlying this regulation largely remains unclear. Read More

View Article and Full-Text PDF