11,701 results match your criteria binding microtubules

Microtubule Bundling Assay under Physiological Conditions.

Bio Protoc 2017 Apr 5;7(7):e2217. Epub 2017 Apr 5.

Department of Biology, University of Hawaii at Hilo, 200 West Kawili Street, Hilo, Hawaii 96720, USA.

Kinesins play a role in organizing the mitotic spindle through the crosslinking of microtubules (MTs), made possible through binding sites at opposite ends of the holoenzyme. Here, we developed a method to test kinesin MT crosslinking action under physiological conditions. Read More

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The motor domain of testis-enriched kinesin KIF9 is essential for its localization in the mouse flagellum.

Exp Anim 2021 Sep 15. Epub 2021 Sep 15.

Research Institute for Microbial Diseases, Osaka University.

Kinesin is a molecular motor that moves along microtubules. Testis-enriched kinesin KIF9 (Kinesin family member 9) is localized in the mouse sperm flagellum and is important for normal sperm motility and male fertility; however, it is unclear if the motor domain of KIF9 is involved in these processes. In this study, we substituted threonine of the ATP binding motif in the KIF9 motor domain to asparagine (T100N) in mice using the CRISPR/Cas9 system, which is known to impair kinesin motor activity. Read More

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September 2021

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors.

Drug Dev Res 2021 Sep 15. Epub 2021 Sep 15.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Giza, Egypt.

Microtubules and the mitotic spindle have become an important target for cancer treatment due to their critical role in cell division. In this work, a novel series of benzofuran and indole derivatives were designed and synthesized, to be evaluated as tubulin polymerization inhibitors. 2-Acetylbenzofuran derivatives 1a,b and 3-acetylindole 1c were condensed with Wittig reagents 2a-d and Wittig-Horner reagents 3a-e to afford the respective 2-ethylidene derivatives 5a-j and 7a-e. Read More

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September 2021

A new class of cytotoxic agents targets tubulin and disrupts microtubule dynamics.

Bioorg Chem 2021 Aug 30;116:105297. Epub 2021 Aug 30.

Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, 2801, W. Bancroft Street, Toledo, OH-43606, USA. Electronic address:

Despite the advances in treatment strategies, cancer is still the second leading cause of death in the USA. A majority of the currently used cancer drugs have limitations in their clinical use due to poor selectivity, toxic side effects and multiple drug resistance, warranting the development of new anticancer drugs of different mechanisms of action. Here we describe the design, synthesis and initial biological evaluation of a new class of antimitotic agents that modulate tubulin polymerization. Read More

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Macrothrombocytopenia of Takenouchi-Kosaki syndrome is ameliorated by CDC42 specific- and lipidation inhibitors in MEG-01 cells.

Sci Rep 2021 Sep 9;11(1):17990. Epub 2021 Sep 9.

Department of Molecular Medicine, Research Institute, Osaka Women's and Children's Hospital, 840 Murodo-cho, Izumi, Osaka, 594-1101, Japan.

Macrothrombocytopenia is a common pathology of missense mutations in genes regulating actin dynamics. Takenouchi-Kosaki syndrome (TKS) harboring the c.191A > G, Tyr64Cys (Y64C) variant in Cdc42 exhibits a variety of clinical manifestations, including immunological and hematological anomalies. Read More

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September 2021

Towards Quantum-Chemical Modeling of the Activity of Anesthetic Compounds.

Int J Mol Sci 2021 Aug 27;22(17). Epub 2021 Aug 27.

Faculty of Mathematics and Natural Sciences, Cardinal Stefan Wyszynski University, Wójcickiego 1/3, 01-938 Warsaw, Poland.

The modeling of the activity of anesthetics is a real challenge because of their unique electronic and structural characteristics. Microscopic approaches relevant to the typical features of these systems have been developed based on the advancements in the theory of intermolecular interactions. By stressing the quantum chemical point of view, here, we review the advances in the field highlighting differences and similarities among the chemicals within this group. Read More

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Therapeutic potential of pregnenolone and pregnenolone methyl ether on depressive and CDKL5 deficiency disorders: Focus on microtubule targeting.

J Neuroendocrinol 2021 Aug 19:e13033. Epub 2021 Aug 19.

Department of Biotechnology and Life Sciences, (DBSV), Centre of NeuroScience, University of Insubria, Busto Arsizio, Italy.

Pregnenolone methyl-ether (PME) is a synthetic derivative of the endogenous neuroactive steroid pregnenolone (PREG), which is an important modulator of several brain functions. In addition to being the precursor of steroids, PREG acts directly on various targets including microtubules (MTs), the functioning of which is fundamental for the development and homeostasis of nervous system. The coordination of MT dynamics is supported by a plethora of MT-associated proteins (MAPs) and by a specific MT code that is defined by the post-translational modifications of tubulin. Read More

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Identification of novel microtubule inhibitors effective in fission yeast and human cells and their effects on breast cancer cell lines.

Open Biol 2021 Sep 8;11(9):210161. Epub 2021 Sep 8.

Laboratory of Yeast Genetics and Cell Biology, Rockefeller University, New York, NY 10065, USA.

Microtubules are critical for a variety of cellular processes such as chromosome segregation, intracellular transport and cell shape. Drugs against microtubules have been widely used in cancer chemotherapies, though the acquisition of drug resistance has been a significant issue for their use. To identify novel small molecules that inhibit microtubule organization, we conducted sequential phenotypic screening of fission yeast and human cells. Read More

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September 2021

Microtubule associated proteins as targets for anticancer drug development.

Bioorg Chem 2021 Sep 1;116:105320. Epub 2021 Sep 1.

CSIR-Central Institute of Medicinal and Aromatics Plants (CSIR-CIMAP) P.O. CIMAP, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address:

The dynamic equilibrium of tubulin-microtubule is an essential aspect of cell survivality. Modulation of this dynamics has become an important target for the cancer drug development. Tubulin exists in the alpha-beta dimer form which polymerizes to form microtubule and further depolymerizes back to tubulin dimer. Read More

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September 2021

In vivo evaluation of a microtubule PET ligand, [C]MPC-6827, in mice following chronic alcohol consumption.

Pharmacol Rep 2021 Sep 7. Epub 2021 Sep 7.

Area of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Manhattan, NY, USA.

Background: Excessive alcohol consumption is a global health burden and requires a better understanding of its neurobiology. A lower density of brain microtubules is found in alcohol-related human brain disease postmortem and in rodent models of chronic alcohol consumption. Here, we report in vivo imaging studies of microtubules in brain using our recently reported Positron Emission Tomography (PET) tracer, [C]MPC-6827, in chronic alcohol-consuming adult male C57BL/6 J mice and control mice. Read More

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September 2021

Potential colchicine binding site inhibitors unraveled by virtual screening, molecular dynamics and MM/PBSA.

Comput Biol Med 2021 Aug 28;137:104817. Epub 2021 Aug 28.

Computational Laboratory of Pharmaceutical Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Do Café, S/n, Ribeirão Preto, SP, 14040-903, Brazil; Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901, Ribeirão Preto, SP, Brazil.

Microtubules have been widely studied in recent decades as an important pharmacological target for the treatment of cancer especially due to its key role in the mitosis process. Among the constituents of the microtubules, αβ-tubulin dimers stand out in view of their four distinct interaction sites, including the so-called colchicine binding site (CBS) - a promising target for the development of new tubulin modulators. When compared to other tubulin sites, targeting the CBS is advantageous because this site is able to host ligands with lower molecular volume and lipophilicity, thus reducing the chances of entailing the phenomenon of multiple drug resistance (MDR) - one of the main reasons of failure in chemotherapy. Read More

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Homology modelling, molecular dynamics simulation and docking evaluation of β-tubulin of Schistosoma mansoni.

Biophys Chem 2021 Aug 16;278:106660. Epub 2021 Aug 16.

Department of Medical Parasitology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.

Schistosomiasis is one of the neglected diseases causing considerable morbidity and mortality throughout the world. Microtubules with its main component, tubulin play a vital role in helminthes including schistosomes. Benzimidazoles represent potential drug candidates by binding β-tubulin. Read More

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The drebrin/EB3 pathway regulates cytoskeletal dynamics to drive neuritogenesis in embryonic cortical neurons.

J Neurochem 2021 Sep 3. Epub 2021 Sep 3.

Centre for Developmental Neurobiology, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.

Co-ordinating the dynamic behaviour of actin filaments (F-actin) and microtubules in filopodia is an important underlying process in neuritogenesis, but the molecular pathways involved are ill-defined. The drebrin/end-binding protein 3 (EB3) pathway is a candidate pathway for linking F-actin to microtubules in filopodia. Drebrin binds F-actin and, simultaneously, the microtubule-binding protein EB3 when bound to microtubule plus-ends. Read More

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September 2021

Cytoskeleton and Associated Proteins: Pleiotropic JNK Substrates and Regulators.

Int J Mol Sci 2021 Aug 4;22(16). Epub 2021 Aug 4.

Université Paris-Saclay, INSERM UMR-S-1193, 5 Rue Jean-Baptiste Clément, 92296 Châtenay-Malabry, France.

This review extensively reports data from the literature concerning the complex relationships between the stress-induced c-Jun N-terminal kinases (JNKs) and the four main cytoskeleton elements, which are actin filaments, microtubules, intermediate filaments, and septins. To a lesser extent, we also focused on the two membrane-associated cytoskeletons spectrin and ESCRT-III. We gather the mechanisms controlling cytoskeleton-associated JNK activation and the known cytoskeleton-related substrates directly phosphorylated by JNK. Read More

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Cytoskeletal Arrest: An Anoxia Tolerance Mechanism.

Metabolites 2021 Aug 23;11(8). Epub 2021 Aug 23.

Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.

Polymerization of actin filaments and microtubules constitutes a ubiquitous demand for cellular adenosine-5'-triphosphate (ATP) and guanosine-5'-triphosphate (GTP). In anoxia-tolerant animals, ATP consumption is minimized during overwintering conditions, but little is known about the role of cell structure in anoxia tolerance. Studies of overwintering mammals have revealed that microtubule stability in neurites is reduced at low temperature, resulting in withdrawal of neurites and reduced abundance of excitatory synapses. Read More

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Matrix stiffness regulates α-TAT1-mediated acetylation of α-tubulin and promotes silica-induced epithelial-mesenchymal transition via DNA damage.

J Cell Sci 2021 01 27;134(2). Epub 2021 Jan 27.

School of Public Health, Medical Research Center, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan 063210, China.

Silicosis is characterized by silica exposure-induced lung interstitial fibrosis and formation of silicotic nodules, resulting in lung stiffening. The acetylation of microtubules mediated by α-tubulin N-acetyltransferase 1 (α-TAT1) is a posttranslational modification that promotes microtubule stability in response to mechanical stimulation. α-TAT1 and downstream acetylated α-tubulin (Ac-α-Tub) are decreased in silicosis, promoting the epithelial-mesenchymal transition (EMT); however, the underlying mechanisms are unknown. Read More

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January 2021

The role of Colchicine on actin polymerization dynamics: as a potent anti-angiogenic factor.

J Biomol Struct Dyn 2021 Aug 23:1-15. Epub 2021 Aug 23.

School of Chemical Sciences, UM-DAE Center for excellence in basic sciences, University of Mumbai, Mumbai, Maharashtra, India.

Over the years, cancer research has focused on different strategies to discover drugs and therapies to treat the metastatic stage of cancer. This stage depends upon the type, and the cause of cancer. One of the central facts about any cancer invasion is the formation of new blood vessels that provide nutrients to these uncontrollably dividing cells. Read More

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Functional roles of α-, α-, β-, β-tubulin in vegetative growth, microtubule assembly and sexual reproduction of .

Appl Environ Microbiol 2021 Aug 11:AEM0096721. Epub 2021 Aug 11.

College of Plant Protection, Nanjing Agricultural University, Nanjing, China.

The plant pathogen contains two α-tubulin (α and α) isotypes and two β-tubulin isotypes (β and β). The functional roles of these tubulins in microtubule assembly are not clear. Previous studies showed that α- and β-tubulin deletion mutants showed severe growth defects and hypersensitivity to carbendazim, which have not been well explained. Read More

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Cryo-EM structure of a microtubule-bound parasite kinesin motor and implications for its mechanism and inhibition.

J Biol Chem 2021 Aug 7:101063. Epub 2021 Aug 7.

Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck, University of London, London, UK. Electronic address:

Plasmodium parasites cause malaria and are responsible annually for hundreds of thousands of deaths. Kinesins are a superfamily of microtubule-dependent ATPases that play important roles in the parasite replicative machinery, which is a potential target for anti-parasite drugs. Kinesin-5, a molecular motor that crosslinks microtubules, is an established anti-mitotic targets in other disease contexts, but its mechanism in P. Read More

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The Microtubule Minus-End Binding Protein Patronin Is Required for the Epithelial Remodeling in the Abdomen.

Front Cell Dev Biol 2021 21;9:682083. Epub 2021 Jul 21.

Interfaculty Centre 'Cells in Motion,' University of Münster, Münster, Germany.

In the developing abdomen, the epithelial tissue displays extensive cytoskeletal remodeling. In stark contrast to the spatio-temporal control of the actin cytoskeleton, the regulation of microtubule architecture during epithelial morphogenesis has remained opaque. In particular, its role in cell motility remains unclear. Read More

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Phylogeny and structural peculiarities of the EB proteins of diatoms.

J Struct Biol 2021 09 6;213(3):107775. Epub 2021 Aug 6.

Limnological Institute, Siberian Branch, Russian Academy of Sciences, Irkutsk, Russia. Electronic address:

The end-binding proteins are a family of microtubule-associated proteins; this family belongs to plus-end-tracking proteins (+TIPs) that regulate microtubule growth and stabilisation. Although the genes encoding EB proteins are found in all eukaryotic genomes, most studies of them have centred on one or another taxonomic group, without a broad comparative analysis. Here, we present a first phylogenetic analysis and a comparative analysis of domain structures of diatom EB proteins in comparison with other phyla of Chromista, red and green algae, as well as model organisms A. Read More

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September 2021

Three-color single-molecule imaging reveals conformational dynamics of dynein undergoing motility.

Proc Natl Acad Sci U S A 2021 Aug;118(31)

HHMI, University of California, San Francisco, CA 94158;

The motor protein dynein undergoes coordinated conformational changes of its domains during motility along microtubules. Previous single-molecule studies analyzed the motion of the AAA rings of the dynein homodimer, but not the distal microtubule-binding domains (MTBDs) that step along the track. Here, we simultaneously tracked with nanometer precision two MTBDs and one AAA ring of a single dynein as it underwent hundreds of steps using three-color imaging. Read More

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Mitochondrial adaptor TRAK2 activates and functionally links opposing kinesin and dynein motors.

Nat Commun 2021 07 28;12(1):4578. Epub 2021 Jul 28.

Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

Mitochondria are transported along microtubules by opposing kinesin and dynein motors. Kinesin-1 and dynein-dynactin are linked to mitochondria by TRAK proteins, but it is unclear how TRAKs coordinate these motors. We used single-molecule imaging of cell lysates to show that TRAK2 robustly activates kinesin-1 for transport toward the microtubule plus-end. Read More

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Phospho-regulated Bim1/EB1 interactions trigger Dam1c ring assembly at the budding yeast outer kinetochore.

EMBO J 2021 Sep 27;40(18):e108004. Epub 2021 Jul 27.

Department of Molecular Genetics I, Center of Molecular Biotechnology, University of Duisburg-Essen, Essen, Germany.

Kinetochores form the link between chromosomes and microtubules of the mitotic spindle. The heterodecameric Dam1 complex (Dam1c) is a major component of the Saccharomyces cerevisiae outer kinetochore, assembling into 3 MDa-sized microtubule-embracing rings, but how ring assembly is specifically initiated in vivo remains to be understood. Here, we describe a molecular pathway that provides local control of ring assembly during the establishment of sister kinetochore bi-orientation. Read More

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September 2021

Autoregulatory control of microtubule binding in doublecortin-like kinase 1.

Elife 2021 07 26;10. Epub 2021 Jul 26.

Department of Molecular and Cellular Biology, University of California, Davis, Davis, United States.

The microtubule-associated protein, doublecortin-like kinase 1 (DCLK1), is highly expressed in a range of cancers and is a prominent therapeutic target for kinase inhibitors. The physiological roles of DCLK1 kinase activity and how it is regulated remain elusive. Here, we analyze the role of mammalian DCLK1 kinase activity in regulating microtubule binding. Read More

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Cdc4 phospho-degrons allow differential regulation of Ame1 protein stability across the cell cycle.

Elife 2021 07 26;10. Epub 2021 Jul 26.

Department of Molecular Genetics I, Faculty of Biology, Center of Medical Biotechnology, University of Duisburg-Essen, Essen, Germany.

Kinetochores are multi-subunit protein assemblies that link chromosomes to microtubules of the mitotic and meiotic spindle. It is still poorly understood how efficient, centromere-dependent kinetochore assembly is accomplished from hundreds of individual protein building blocks in a cell cycle-dependent manner. Here, by combining comprehensive phosphorylation analysis of native Ctf19 subunits with biochemical and functional assays in the model system budding yeast, we demonstrate that Cdk1 phosphorylation activates phospho-degrons on the essential subunit Ame1, which are recognized by the E3 ubiquitin ligase complex SCF-Cdc4. Read More

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Interaction of spindle assembly factor TPX2 with importins-α/β inhibits protein phase separation.

J Biol Chem 2021 Jul 21;297(3):100998. Epub 2021 Jul 21.

Department of Molecular Biology, Princeton University, Princeton, New Jersey, USA. Electronic address:

The microtubule-based mitotic spindle is responsible for equally partitioning the genome during each cell division, and its assembly is executed via several microtubule nucleation pathways. Targeting Protein for XKlp2 (TPX2) stimulates the branching microtubule nucleation pathway, where new microtubules are nucleated from preexisting ones within mitotic or meiotic spindles. TPX2, like other spindle assembly factors, is sequestered by binding to nuclear importins-α/β until the onset of mitosis, yet the molecular nature of this regulation remains unclear. Read More

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ER - lysosome contacts at a pre-axonal region regulate axonal lysosome availability.

Nat Commun 2021 07 23;12(1):4493. Epub 2021 Jul 23.

Cell Biology, Neurobiology and Biophysics. Department of Biology, Faculty of Science, Utrecht University, Utrecht, The Netherlands.

Neuronal function relies on careful coordination of organelle organization and transport. Kinesin-1 mediates transport of the endoplasmic reticulum (ER) and lysosomes into the axon and it is increasingly recognized that contacts between the ER and lysosomes influence organelle organization. However, it is unclear how organelle organization, inter-organelle communication and transport are linked and how this contributes to local organelle availability in neurons. Read More

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Analysis of the Structural Mechanism of ATP Inhibition at the AAA1 Subunit of Cytoplasmic Dynein-1 Using a Chemical "Toolkit".

Int J Mol Sci 2021 Jul 19;22(14). Epub 2021 Jul 19.

School of Pharmacy, Memorial University of Newfoundland, 300 Prince Philip Dr, St. John's, NL A1B 3V6, Canada.

Dynein is a ~1.2 MDa cytoskeletal motor protein that carries organelles via retrograde transport in eukaryotic cells. The motor protein belongs to the ATPase family of proteins associated with diverse cellular activities and plays a critical role in transporting cargoes to the minus end of the microtubules. Read More

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Transcriptome Profile Analysis of Triple-Negative Breast Cancer Cells in Response to a Novel Cytostatic Tetrahydroisoquinoline Compared to Paclitaxel.

Int J Mol Sci 2021 Jul 19;22(14). Epub 2021 Jul 19.

Pharmaceutical Sciences Division, College of Pharmacy & Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA.

The absence of chemotherapeutic target hormone receptors in breast cancer is descriptive of the commonly known triple-negative breast cancer (TNBC) subtype. TNBC remains one of the most aggressive invasive breast cancers, with the highest mortality rates in African American women. Therefore, new drug therapies are continually being explored. Read More

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