8,350 results match your criteria microtubule dynamics

Micron-scale geometrical features of microtubules as regulators of microtubule organization.

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

Department of Molecular Biology, Massachusetts General Hospital, Boston, United States.

The organization of micron-sized, multi-microtubule arrays from individual microtubules is essential for diverse cellular functions. The microtubule polymer is largely viewed as a passive building block during the organization process. An exception is the 'tubulin code' where alterations to tubulin at the amino acid level can influence the activity of microtubule-associated proteins. Read More

View Article and Full-Text PDF

Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU.

Front Neurosci 2021 25;15:643115. Epub 2021 May 25.

Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.

In the adult human brain, six isoforms of the microtubule-associated protein TAU are expressed, which result from alternative splicing of exons 2, 3, and 10 of the gene. These isoforms differ in the number of N-terminal inserts (0N, 1N, 2N) and C-terminal repeat domains (3R or 4R) and are differentially expressed depending on the brain region and developmental stage. Although all TAU isoforms can aggregate and form neurofibrillary tangles, some tauopathies, such as Pick's disease and progressive supranuclear palsy, are characterized by the accumulation of specific TAU isoforms. Read More

View Article and Full-Text PDF

Coupling of dynamic microtubules to F-actin by Fmn2 regulates chemotaxis of neuronal growth cones.

J Cell Sci 2021 Jun 9. Epub 2021 Jun 9.

Indian Institute of Science Education and Research (IISER) Pune, Dr Homi Bhabha Road, Pune 411008, India.

Dynamic co-regulation of the actin and microtubule subsystems enables the highly precise and adaptive remodelling of the cytoskeleton necessary for critical cellular processes, like axonal pathfinding. The modes and mediators of this interpolymer crosstalk, however, are inadequately understood. We identify Fmn2, a non-diaphanous related formin associated with cognitive disabilities, as a novel regulator of cooperative actin-microtubule remodelling in growth cones. Read More

View Article and Full-Text PDF

Planar polarization of cilia in the zebrafish floor-plate involves Par3-mediated posterior localization of highly motile basal bodies.

Development 2021 Jun 9. Epub 2021 Jun 9.

Sorbonne Université, CNRS UMR7622, INSERM U1156, Institut de Biologie Paris Seine (IBPS) - Developmental Biology Unit, 75005, Paris, France.

Epithelial cilia, whether motile or primary, often display an off-centered planar localization within the apical cell surface. This form of planar cell polarity (PCP) involves the asymmetric positioning of the ciliary basal body (BB). Using the mono-ciliated epithelium of the embryonic zebrafish floor-plate, we investigated the dynamics and mechanisms of BB polarization by live-imaging. Read More

View Article and Full-Text PDF

[Research progress on anti-tumor mechanism of tumor treating fields].

Zhonghua Wai Ke Za Zhi 2021 Jun;59(6):558-560

Department of Neurosurgery,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China.

The anti-tumor mechanism of tumor treating fields (TTFields) is mainly through interfering with the dynamics of microtubule subunits in mitosis,which blocks the normal process of cell division and eventually leads to cell death.In recent years,relevant studies have found that TTFields still have immunological,molecular biological and other related anti-tumor mechanisms,and can induce reversible increase of cell membrane and blood-brain barrier permeability,which plays a synergistic role in combination with anti-tumor drugs.With the development of multi-system research,the specific treatment frequency,time and field strength of TTFields in different tumor treatments will be revealed. Read More

View Article and Full-Text PDF

Mechano-induced cell metabolism promotes microtubule glutamylation to force metastasis.

Cell Metab 2021 May 31. Epub 2021 May 31.

Université Côte d'Azur, CNRS, IPMC, Valbonne, France. Electronic address:

Mechanical signals from the tumor microenvironment modulate cell mechanics and influence cell metabolism to promote cancer aggressiveness. Cells withstand external forces by adjusting the stiffness of their cytoskeleton. Microtubules (MTs) act as compression-bearing elements. Read More

View Article and Full-Text PDF

Goldberg-Shprintzen syndrome protein KIF1BP is a CITK interactor implicated in cytokinesis.

J Cell Sci 2021 Jun 8;134(11). Epub 2021 Jun 8.

Neuroscience Institute Cavalieri Ottolenghi, Turin 10123, Italy.

Goldberg-Shprintzen disease (GOSHS) is a rare microcephaly syndrome accompanied by intellectual disability, dysmorphic facial features, peripheral neuropathy and Hirschsprung disease. It is associated with recessive mutations in the gene encoding kinesin family member 1-binding protein (KIF1BP, also known as KIFBP). The encoded protein regulates axon microtubules dynamics, kinesin attachment and mitochondrial biogenesis, but it is not clear how its loss could lead to microcephaly. Read More

View Article and Full-Text PDF

The inhibition of microtubule dynamics instability alters lipid homeostasis in TM4 Sertoli cells.

Toxicol Appl Pharmacol 2021 Jun 2;426:115607. Epub 2021 Jun 2.

Instituto de Investigaciones Bioquıímicas de Bahía Blanca, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Universidad Nacional del Sur (UNS), Bahía Blanca, Argentina.

Sertoli cells (SC) structurally support and transport nutrients to germ cells during spermatogenesis facilitated by an active cytoskeleton. Chemical perturbation of SC microtubule (MT) dynamics instability leads to premature germ cell exfoliation demonstrating that this process is essential for male fertility, yet the effects of MT damaging drugs on SC lipid metabolism have been less explored. The aim of this study was to advance our understanding of how adequate SC MT dynamicity is needed to finely tune lipid homeostasis. Read More

View Article and Full-Text PDF

Conformation and dynamics of the kinase domain drive subcellular location and activation of LRRK2.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093;

To explore how pathogenic mutations of the multidomain leucine-rich repeat kinase 2 (LRRK2) hijack its finely tuned activation process and drive Parkinson's disease (PD), we used a multitiered approach. Most mutations mimic Rab-mediated activation by "unleashing" kinase activity, and many, like the kinase inhibitor MLi-2, trap LRRK2 onto microtubules. Here we mimic activation by simply deleting the inhibitory N-terminal domains and then characterize conformational changes induced by MLi-2 and PD mutations. 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

Analyzing Centrioles and Cilia by Expansion Microscopy.

Methods Mol Biol 2021 ;2329:249-263

Laboratory of Protein Dynamics and Signaling, NIH/NCI/CCR, Frederick, MD, USA.

Expansion microscopy is an imaging method based on isotropic physical expansion of biological samples, which improves optical resolution and allows imaging of subresolutional cellular components by conventional microscopes. Centrioles are small microtubule-based cylindrical structures that build centrosomes and cilia, two organelles essential for vertebrates. Due to a centriole's small size, electron microscopy has traditionally been used to study centriole length and ultrastructural features. Read More

View Article and Full-Text PDF
January 2021

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

Inhibition of cell expansion enhances cortical microtubule stability in the root apex of Arabidopsis thaliana.

J Biol Res (Thessalon) 2021 Jun 3;28(1):13. Epub 2021 Jun 3.

Department of Botany, School of Biology, Aristotle University of Thessaloniki, 541 24, Thessaloniki, Greece.

Background: Cortical microtubules regulate cell expansion by determining cellulose microfibril orientation in the root apex of Arabidopsis thaliana. While the regulation of cell wall properties by cortical microtubules is well studied, the data on the influence of cell wall to cortical microtubule organization and stability remain scarce. Studies on cellulose biosynthesis mutants revealed that cortical microtubules depend on Cellulose Synthase A (CESA) function and/or cell expansion. 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

NEK9 regulates primary cilia formation by acting as a selective autophagy adaptor for MYH9/myosin IIA.

Nat Commun 2021 06 2;12(1):3292. Epub 2021 Jun 2.

Department of Biochemistry and Molecular Biology, The University of Tokyo, Tokyo, Japan.

Autophagy regulates primary cilia formation, but the underlying mechanism is not fully understood. In this study, we identify NIMA-related kinase 9 (NEK9) as a GABARAPs-interacting protein and find that NEK9 and its LC3-interacting region (LIR) are required for primary cilia formation. Mutation in the LIR of NEK9 in mice also impairs in vivo cilia formation in the kidneys. Read More

View Article and Full-Text PDF

C118P, a novel microtubule inhibitor with anti-angiogenic and vascular disrupting activities, exerts anti-tumor effects against hepatocellular carcinoma.

Biochem Pharmacol 2021 May 30:114641. Epub 2021 May 30.

Department of Pharmacy, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai, 519000 China.

Hepatocellular carcinoma (HCC), a hypervascular solid tumor, is the most leading cause of cancer mortality worldwide. Microtubule binding agents targeting tumor vasculature have been investigated and employed clinically. C118P is a newly synthesized analog of CA4 with improved water solubility and extended half-life. Read More

View Article and Full-Text PDF

LMBD1 protein participates in cell mitosis by regulating microtubule assembly.

Biochem J 2021 Jun 2. Epub 2021 Jun 2.

National Taiwan University, Taipei, Taiwan.

LMBD1 was previously demonstrated to regulate the endocytosis of insulin receptor on cell surface and to mediate the export of cobalamin from the lysosomes to cytosol, but little is known about its function in mitosis. In this study, interactome analysis data indicate that LMBD1 is involved in cytoskeleton regulation. Both immunoprecipitation and GST pulldown assays demonstrated association of LMBD1 with tubulin. Read More

View Article and Full-Text PDF

EFA6 in Axon Regeneration, as a Microtubule Regulator and as a Guanine Nucleotide Exchange Factor.

Cells 2021 May 26;10(6). Epub 2021 May 26.

Barshop Institute for Longevity and Aging Studies, Department of Cell Systems and Anatomy, UT Health San Antonio, San Antonio, TX 78229, USA.

Axon regeneration after injury is a conserved biological process that involves a large number of molecular pathways, including rapid calcium influx at injury sites, retrograde injury signaling, epigenetic transition, transcriptional reprogramming, polarized transport, and cytoskeleton reorganization. Despite the numerous efforts devoted to understanding the underlying cellular and molecular mechanisms of axon regeneration, the search continues for effective target molecules for improving axon regeneration. Although there have been significant historical efforts towards characterizing pro-regenerative factors involved in axon regeneration, the pursuit of intrinsic inhibitors is relatively recent. 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

Dynamic posttranslational modifications of cytoskeletal proteins unveil hot spots under nitroxidative stress.

Redox Biol 2021 Aug 24;44:102014. Epub 2021 May 24.

Institute of Bioanalytical Chemistry, Faculty of Chemistry and Mineralogy, Germany; Center for Biotechnology and Biomedicine, University of Leipzig, Deutscher Platz 5, 04103, Leipzig, Germany. Electronic address:

The cytoskeleton is a supramolecular structure consisting of interacting protein networks that support cell dynamics in essential processes such as migration and division, as well as in responses to stress. Fast cytoskeletal remodeling is achieved with the participation of regulatory proteins and posttranslational modifications (PTMs). Redox-related PTMs are emerging as critical players in cytoskeletal regulation. Read More

View Article and Full-Text PDF

Tau mis-splicing correlates with motor impairments and striatal dysfunction in a model of tauopathy.

Brain 2021 Jun 1. Epub 2021 Jun 1.

Instituto de Investigaciones en Ingeniería Genética y Biología Molecular (INGEBI-CONICET), Buenos Aires, Argentina.

Tauopathies are neurodegenerative diseases caused by the abnormal metabolism of the microtubule associated protein Tau, which is highly expressed in neurons and critically involved in microtubule dynamics. In the adult human brain, the alternative splicing of exon 10 in tau pre-mRNA produces equal amounts of protein isoforms with either three (3 R) or four (4 R) microtubule binding domains. Imbalance in the 3 R : 4 R tau ratio is associated with primary tauopathies that develop atypical parkinsonism, such as Progressive Supranuclear Palsy and Corticobasal Degeneration. Read More

View Article and Full-Text PDF

Bidirectional role of microtubule dynamics in the acquisition and maintenance of temporal information in dorsolateral striatum.

Neurobiol Learn Mem 2021 May 29;183:107468. Epub 2021 May 29.

Department of Psychology and Neuroscience, Duke University, Durham, NC, United States.

Accurate and precise timing is crucial for complex and purposeful behaviors, such as foraging for food or playing a musical instrument. The brain is capable of processing temporal information in a coordinated manner, as if it contains an 'internal clock'. Similar to the need for the brain to orient itself in space in order to understand its surroundings, temporal orientation and tracking is an essential component of cognition as well. 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

When the autophagy protein ATG16L1 met the ciliary protein IFT20.

Autophagy 2021 May 31:1-3. Epub 2021 May 31.

Institut Necker-Enfants Malades (INEM), Université de Paris, Paris, France.

The primary cilium (PC), a plasma membrane microtubule-based structure, is a sensor of extracellular chemical and mechanical stress stimuli. Upon ciliogenesis, the autophagy protein ATG16L1 and the ciliary protein IFT20 are co-transported to the PC. We demonstrated in a recent study that IFT20 and ATG16L1 interact in a multiprotein complex. Read More

View Article and Full-Text PDF

Ecm29-Dependent Proteasome Localization Regulates Cytoskeleton Remodeling at the Immune Synapse.

Front Cell Dev Biol 2021 13;9:650817. Epub 2021 May 13.

Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.

The formation of an immune synapse (IS) enables B cells to capture membrane-tethered antigens, where cortical actin cytoskeleton remodeling regulates cell spreading and depletion of F-actin at the centrosome promotes the recruitment of lysosomes to facilitate antigen extraction. How B cells regulate both pools of actin, remains poorly understood. We report here that decreased F-actin at the centrosome and IS relies on the distribution of the proteasome, regulated by Ecm29. 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

Synthesis of new 2-aminothiazolyl/benzothiazolyl-based 3,4-dihydropyrimidinones and evaluation of their effects on adenocarcinoma gastric cell migration.

Mol Divers 2021 May 29. Epub 2021 May 29.

Department of Medicinal Chemistry, School of Pharmacy, Ardabil University of Medical Sciences, 5618953141, Ardabil, Iran.

Gastric cancer is one of the malignant tumors of the gastrointestinal tract that, despite its decrease in recent years, is still the fourth most common cancer and the second leading cause of cancer-related death. Various strategies including chemotherapy are used to keep cancer cells from spreading and induce apoptotic death in them. Recent studies have shown that dihydropyrimidinones (DHPMs) are privileged structures in medicinal chemistry due to their pharmacological effects. Read More

View Article and Full-Text PDF

Live-Cell Fluorescence Imaging of Microtubules by Using a Tau-Derived Peptide.

Methods Mol Biol 2021 ;2274:169-179

Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, Tottori, Japan.

Microtubules (MTs) are important targets for imaging in living cells because of their vital roles in cellular processes. The dynamics (polymerization/depolymerization) of MTs has been imaged in living cells by utilizing MT-targeted drugs as scaffolds. We previously developed a unique MT-binding motif derived from a MT-associated protein, Tau. Read More

View Article and Full-Text PDF
January 2021

Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool.

Commun Biol 2021 May 28;4(1):640. Epub 2021 May 28.

Department of Pharmacology, University of Cambridge, Cambridge, UK.

Targeted protein degradation tools are becoming a new therapeutic modality, allowing small molecule ligands to be reformulated as heterobifunctional molecules (PROteolysis Targeting Chimeras, PROTACs) that recruit ubiquitin ligases to targets of interest, leading to ubiquitination and destruction of the targets. Several PROTACs against targets of clinical interest have been described, but detailed descriptions of the cell biology modulated by PROTACs are missing from the literature. Here we describe the functional characterization of a PROTAC derived from AURKA inhibitor MLN8237 (alisertib). Read More

View Article and Full-Text PDF