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Journal of Nanobiotechnology Dec 2020Microtubules and carbon nanotubes (CNTs), and more particularly multi-walled CNTs (MWCNTs), share many mechanical and morphological similarities that prompt their... (Review)
Review
Microtubules and carbon nanotubes (CNTs), and more particularly multi-walled CNTs (MWCNTs), share many mechanical and morphological similarities that prompt their association into biosynthetic tubulin filaments both, in vitro and in vivo. Unlike CNTs, microtubules are highly dynamic protein polymers that, upon interaction with these nanomaterials, display enhanced stability that has critical consequences at the cellular level. Among others, CNTs prompt ectopic (acentrosomal) microtubule nucleation and the disassembly of the centrosome, causing a dramatic cytoskeletal reorganization. These changes in the microtubule pattern trigger the generation of ineffective biomechanical forces that result in migration defects, and ultimately in spindle-assembly checkpoint (SAC) blockage and apoptosis. In this review, we describe the molecular mechanism involved in the intrinsic interference of CNTs with the microtubule dynamics and illustrate the consequences of this effect on cell biomechanics. We also discuss the potential application of these synthetic microtubule-stabilizing agents as synergetic agents to boost the effect of classical chemotherapy that includes spindle poisons (i.e. paclitaxel) or DNA interfering agents (5-fluorouracil)-, and list some of the advantages of the use of MWCNTs as adjuvant agents in preventing cell resistance to chemotherapy.
Topics: Apoptosis; Cell Cycle; Centrosome; Cytoskeleton; Humans; Microtubules; Nanotubes, Carbon; Neoplasms; Paclitaxel; Phenotype; Tubulin
PubMed: 33317574
DOI: 10.1186/s12951-020-00742-y -
Developmental Neurobiology Apr 2015Synaptic plasticity is a hallmark of the nervous system and is thought to be integral to higher brain functions such as learning and memory. Calcium, acting as a second... (Review)
Review
Synaptic plasticity is a hallmark of the nervous system and is thought to be integral to higher brain functions such as learning and memory. Calcium, acting as a second messenger, and the calcium/calmodulin dependent kinase CaMKII are key regulators of neuronal plasticity. Given the importance of the actin and microtubule (MT) cytoskeleton in dendritic spine morphology, composition and plasticity, it is not surprising that many regulators of these cytoskeletal elements are downstream of the CaMKII pathway. In this review, we discuss the emerging role of calcium and CaMKII in the regulation of MTs and cargo unloading during synaptic plasticity.
Topics: Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cytoskeleton; Microtubules; Signal Transduction
PubMed: 25156276
DOI: 10.1002/dneu.22227 -
The Journal of Biological Chemistry Jul 2015Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are... (Review)
Review
Microtubules give rise to intracellular structures with diverse morphologies and dynamics that are crucial for cell division, motility, and differentiation. They are decorated with abundant and chemically diverse posttranslational modifications that modulate their stability and interactions with cellular regulators. These modifications are important for the biogenesis and maintenance of complex microtubule arrays such as those found in spindles, cilia, neuronal processes, and platelets. Here we discuss the nature and subcellular distribution of these posttranslational marks whose patterns have been proposed to constitute a tubulin code that is interpreted by cellular effectors. We review the enzymes responsible for writing the tubulin code, explore their functional consequences, and identify outstanding challenges in deciphering the tubulin code.
Topics: Animals; Humans; Kinetics; Microtubules; Models, Biological; Models, Molecular; Multienzyme Complexes; Peptide Synthases; Protein Multimerization; Protein Processing, Post-Translational; Tubulin
PubMed: 25957412
DOI: 10.1074/jbc.R115.637447 -
Cellular and Molecular Life Sciences :... Feb 2013Interaction of microtubules with kinetochores is fundamental to chromosome segregation. Kinetochores initially associate with lateral surfaces of microtubules and... (Review)
Review
Interaction of microtubules with kinetochores is fundamental to chromosome segregation. Kinetochores initially associate with lateral surfaces of microtubules and subsequently become attached to microtubule ends. During these interactions, kinetochores can move by sliding along microtubules or by moving together with depolymerizing microtubule ends. The interplay between kinetochores and microtubules leads to the establishment of bi-orientation, which is the attachment of sister kinetochores to microtubules from opposite spindle poles, and subsequent chromosome segregation. Molecular mechanisms underlying these processes have been intensively studied over the past 10 years. Emerging evidence suggests that the KNL1-Mis12-Ndc80 (KMN) network plays a central role in connecting kinetochores to microtubules, which is under fine regulation by a mitotic kinase, Aurora B. However, a growing number of additional molecules are being shown to be involved in the kinetochore-microtubule interaction. Here I overview the current range of regulatory mechanisms of the kinetochore-microtubule interaction, and discuss how these multiple molecules contribute cooperatively to allow faithful chromosome segregation.
Topics: Animals; Chromosome Segregation; Humans; Kinetochores; Microtubules; Mitosis; Models, Molecular
PubMed: 22752158
DOI: 10.1007/s00018-012-1057-7 -
Current Opinion in Cell Biology Feb 2019Microtubules are cytoskeletal polymers that dynamically remodel to perform essential cellular functions. Individual microtubules alternate between phases of growth and... (Review)
Review
Microtubules are cytoskeletal polymers that dynamically remodel to perform essential cellular functions. Individual microtubules alternate between phases of growth and shrinkage via sudden transitions called catastrophe and rescue, driven by losing and regaining a stabilizing cap at the dynamic microtubule end. New in vitro studies now show that a conserved family of CLASP proteins specifically modulate microtubule catastrophe and rescue transitions. Further, recent cryo-electron microscopy approaches have elucidated new structural features of the stabilizing cap. Together, these new advances provide a clearer view on the complexity of the microtubule end and its regulation.
Topics: Animals; Cryoelectron Microscopy; Humans; Microtubule-Associated Proteins; Microtubules; Nucleotides; Tubulin
PubMed: 30453184
DOI: 10.1016/j.ceb.2018.10.011 -
Brain : a Journal of Neurology Oct 2013Contemporary research has revealed a great deal of information on the behaviours of microtubules that underlie critical events in the lives of neurons. Microtubules in... (Review)
Review
Contemporary research has revealed a great deal of information on the behaviours of microtubules that underlie critical events in the lives of neurons. Microtubules in the neuron undergo dynamic assembly and disassembly, bundling and splaying, severing, and rapid transport as well as integration with other cytoskeletal elements such as actin filaments. These various behaviours are regulated by signalling pathways that affect microtubule-related proteins such as molecular motor proteins and microtubule severing enzymes, as well as a variety of proteins that promote the assembly, stabilization and bundling of microtubules. In recent years, translational neuroscientists have earmarked microtubules as a promising target for therapy of injury and disease of the nervous system. Proof-of-principle has come mainly from studies using taxol and related drugs to pharmacologically stabilize microtubules in animal models of nerve injury and disease. However, concerns persist that the negative consequences of abnormal microtubule stabilization may outweigh the positive effects. Other potential approaches include microtubule-active drugs with somewhat different properties, but also expanding the therapeutic toolkit to include intervention at the level of microtubule regulatory proteins.
Topics: Animals; Humans; Microtubule-Associated Proteins; Microtubules; Nervous System; Nervous System Diseases; Neurons; Paclitaxel
PubMed: 23811322
DOI: 10.1093/brain/awt153 -
Molecular Biology of the Cell Jul 2022The centriole is a minute cylindrical organelle present in a wide range of eukaryotic species. Most centrioles have a signature ninefold radial symmetry of microtubules...
The centriole is a minute cylindrical organelle present in a wide range of eukaryotic species. Most centrioles have a signature ninefold radial symmetry of microtubules that is imparted to the axonemes of the cilia and flagella they template, with nine centriolar microtubule doublets growing into nine axonemal microtubule doublets. There are exceptions to the ninefold symmetrical arrangement of axonemal microtubules in some species, with lower or higher fold symmetries. In the few cases where this has been examined, such alterations in axonemal symmetries are grounded in similar alterations in centriolar symmetries. Here, we examine the question of microtubule number continuity between centriole and axoneme in flagellated gametes of the gregarine , which have been reported to exhibit a sixfold radial symmetry of axonemal microtubules. We used time-lapse differential interference microscopy to identify the stage at which flagellated gametes are present. Thereafter, using electron microscopy and ultrastructure-expansion microscopy coupled to stimulated emission depletion superresolution imaging, we uncover that a six- or fivefold radial symmetry in the axoneme is accompanied by an eightfold radial symmetry in the centriole. We conclude that the transition between centriolar and axonemal microtubules can be characterized by unexpected plasticity.
Topics: Apicomplexa; Axoneme; Centrioles; Cilia; Flagella; Microtubules
PubMed: 35544302
DOI: 10.1091/mbc.E22-04-0123 -
Scientific Reports Mar 2015Several strategies for controlling microtubule patterns are developed because of the rigidity determined from the molecular structure and the geometrical structure. In...
Several strategies for controlling microtubule patterns are developed because of the rigidity determined from the molecular structure and the geometrical structure. In contrast to the patterns in co-operation with motor proteins or associated proteins, microtubules have a huge potential for patterns via their intrinsic flexural rigidity. We discover that a microtubule teardrop pattern emerges via self-assembly under hydrodynamic flow from the parallel bundles without motor proteins. In the growth process, the bundles ultimately bend according to the critical bending curvature. Such protein pattern formation utilizing the intrinsic flexural rigidity will provide broad understandings of self-assembly of rigid rods, not only in biomolecules, but also in supramolecules.
Topics: Algorithms; Animals; Microscopy, Fluorescence; Microtubules; Models, Theoretical; Rhodamines; Tubulin
PubMed: 25823414
DOI: 10.1038/srep09581 -
Developmental Neurobiology Jun 2011It is widely believed that signature patterns of microtubule polarity orientation within axons and dendrites underlie compositional and morphological differences that... (Review)
Review
It is widely believed that signature patterns of microtubule polarity orientation within axons and dendrites underlie compositional and morphological differences that distinguish these neuronal processes from one another. Axons of vertebrate neurons display uniformly plus-end-distal microtubules, whereas their dendrites display non-uniformly oriented microtubules. Recent studies on insect neurons suggest that it is the minus-end-distal microtubules that are the critical feature of the dendritic microtubule array, whether or not they are accompanied by plus-end-distal microtubules. Discussed in this article are the history of these findings, their implications for the regulation of neuronal polarity across the animal kingdom, and potential mechanisms by which neurons establish the distinct microtubule polarity patterns that define axons and dendrites.
Topics: Animals; Cell Polarity; Humans; Microtubules; Neurons
PubMed: 21557497
DOI: 10.1002/dneu.20818 -
International Journal of Molecular... Jul 2021The general mechanism of controlling, information and organization in biological systems is based on the internal coherent electromagnetic field. The electromagnetic...
The general mechanism of controlling, information and organization in biological systems is based on the internal coherent electromagnetic field. The electromagnetic field is supposed to be generated by microtubules composed of identical tubulin heterodimers with periodic organization and containing electric dipoles. We used a classical dipole theory of generation of the electromagnetic field to analyze the space-time coherence. The structure of microtubules with the helical and axial periodicity enables the interaction of the field in time shifted by one or more periods of oscillation and generation of coherent signals. Inner cavity excitation should provide equal energy distribution in a microtubule. The supplied energy coherently excites oscillators with a high electrical quality, microtubule inner cavity, and electrons at molecular orbitals and in 'semiconduction' and 'conduction' bands. The suggested mechanism is supposed to be a general phenomenon for a large group of helical systems.
Topics: Electromagnetic Fields; Microtubules
PubMed: 34360980
DOI: 10.3390/ijms22158215