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How do neurons age?A focused review on the aging of the microtubular cytoskeleton

Neural Regeneration Research 2024年第9期19卷 1899-1907页

作者： Brad Richardson Thomas Goedert Shmma Quraishe Katrin Deinhardt Amritpal Mudher School of Biological Sciences University of SouthamptonSouthamptonUK Institute of Developmental and Regenerative Medicine University of OxfordOxfordUK

Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain

关键词： age-related changes aging cytoskeleton microtubules neuronal morphology

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Connecting neurodevelopment to neurodegeneration:a spotlight on the role of kinesin superfamily protein 2A(KIF2A)

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Neural Regeneration Research 2024年第2期19卷 375-379页

作者： Nuria Ruiz-Reig Janne Hakanen Fadel Tissir Universitécatholique de Louvain Institute of neuroscienceBrusselsBelgium College of Health and Life Sciences Hamad Bin Khalifa University(HBKU)DohaQatar

microtubules play a central role in cytoskeletal changes during neuronal development and maintenance.Microtubule dynamics is essential to polarity and shape transitions underlying neural cell division,differentiation,motility,and maturation.Kinesin superfamily protein 2A is a member of human kinesin 13 gene family of proteins that depolymerize and destabilize microtubules.In dividing cells,kinesin superfamily protein 2A is involved in mitotic progression,spindle assembly,and chromosome segregation.In postmitotic neurons,it is required for axon/dendrite specification and extension,neuronal migration,connectivity,and survival.Humans with kinesin superfamily protein 2A mutations suffer from a variety of malformations of cortical development,epilepsy,autism spectrum disorder,and neurodegeneration.In this review,we discuss how kinesin superfamily protein 2A regulates neuronal development and function,and how its deregulation causes neurodevelopmental and neurological disorders.

关键词： brain disorders cortical malformations kinesin microtubules neurodegeneration neurodevelopment

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AtMAC stabilizes the phragmoplast by crosslinking microtubules and actin filaments during cytokinesis

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Journal of Integrative Plant Biology 2023年第8期65卷 1950-1965页

作者： Pingzhou Du Yu Liu Lu Deng Dong Qian Xiuhua Xue Ting Yang Tonghui Li Yun Xiang Haiyun Ren Center for Biological Science and Technology Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of EducationZhuhai-Macao Biotechnology Joint LaboratoryAdvanced Institute of Natural ScienceBeijing Normal UniversityZhuhai 519087China MOE Key Laboratory of Cell Activities and Stress Adaptations School of Life SciencesLanzhou UniversityLanzhou 73000oChina

The phragmoplast,a structure crucial for the completion of cytokinesis in plant cells,is composed of antiparallel microtubules(MTs)and actin filaments(AFs).However,how the parallel structure of phragmoplast MTs and AFs is maintained,especially during centrifugal phragmoplast expansion,remains elusive.Here,we analyzed a new Arabidopsis thaliana MT and AF crosslinking protein(AtMAC).When AtMAC was deleted,the phragmoplast showed disintegrity during centrifugal expansion,and the resulting phragmoplast fragmentation led to incomplete cell plates.Overexpression of AtMAC increased the resistance of phragmoplasts to depolymerization and caused the formation of additional phragmoplasts during cytokinesis.Biochemical experiments showed that AtMAC crosslinked MTs and AFs in vitro,and the truncated AtMAC protein,N-CC1,was the key domain controlling the ability of AtMAC.Further analysis showed that N-CC1(51–154)is the key domain for binding MTs,and N-CC1(51–125)for binding AFs.In conclusion,AtMAC is the novel MT and AF crosslinking protein found to be involved in regulation of phragmoplast organization during centrifugal phragmoplast expansion,which is required for complete cytokinesis.

关键词： actin filaments AtMAC cytokinesis phragmoplast microtubules

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microtubules Are Essential for Guard-Cell Function in Vicia and Arabidopsis

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Molecular Plant 2012年第3期5卷 601-610页

作者： William Eisinger David Ehrhardt Winslow Briggs Department of Biology Santa Clara University Santa Clara CA 95053 USA Department of Plant Biology Carnegie Institution for Science Palo Alto CA 94305 USA

Radially arranged cortical microtubules are a prominent feature of guard cells. Guard cells expressing GFP- tubulin showed consistent changes in the appearance of microtubules when stomata opened or closed. Guard cells showed fewer microtubule structures as stomata closed, whether induced by transfer to darkness, ABA, hydrogen per- oxide, or sodium hydrogen carbonate. Guard cells kept in the dark （closed stomata） showed increases in microtubule struc- tures and stomatal aperture on light treatment. GFP-EB1, marking microtubule growing plus ends, showed no change in number of plus ends or velocity of assembly on stomatal closure. Since the number of growing plus ends and the rate of plus-end growth did not change when microtubule structure numbers declined, microtubule instability and/or rearrange- ment must be responsible for the apparent loss of microtubules. Guard cells with closed stomata showed more cytosolic GFP-fluorescence than those with open stomata as cortical microtubules became disassembled, although with a large net loss in total fluorescence. Microtubule-targeted drugs blocked guard-cell function in Vicia and Arabidopsis. Oryzalin dis- rupted guard-cell microtubules and prevented stomatal opening and taxol stabilized guard-cell microtubules and delayed stomatal closure. Gas exchange measurements indicated that the transgenes for fluorescent-labeled proteins did not dis- rupt normal stomatal function. These dynamic changes in guard-cell microtubules combined with our inhibitor studies provide evidence for an active role of microtubules in guard-cell function.

关键词： cytoskeleton dynamics fluorescence imaging guard cells microtubules

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Phosphorylation of Microtubule-associated Protein SB401 from Solanum berthaultii Regulates Its Effect on microtubules

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Journal of Integrative Plant Biology 2009年第3期51卷 235-242页

作者： Bao-Quan Liu Lifeng Jin Lei Zhu Jiejie Li Shuli Huang Ming Yuan State Key Laboratory of Plant Physiology and Biochemistry Department of Plant Sciences College of Biological Sciences China Agricultural University Beijing 100094 China Department of Biological Engineering College of Life Sciences Dalian Nationalities University Dalian 116600 China

We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F-actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation. Our experimental results showed that the phosphorylation of SB401 by casein kinase II （CKII） downregulates the activities of SB401, namely the bundling of microtubules and enhancement of the polymerization of tubulin. However, phosphorylation of SB401 had no observable effect on its bundling of F-actin. Further investigation using extract of potato pollen indicated that a CKIl-like kinase may exist in potato pollen. Antibodies against CKII alpha recognized specifically a major band from the pollen extract and the pollen extract was able to phosphorylate the SB401 protein in vitro. The CKIl-like kinase showed a similar ability to downregulate the bundling of microtubules. Our experiments demonstrated that phosphorylation plays an important role in the regulation of SB401 activity. We propose that this phosphorylation may regulate the effects of SB401 on microtubules and the actin cytoskeleton.

关键词： F-actin microtubule-associated protein microtubules phosphorylation Solanum berthaultii.

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Propagation of kink–antikink pair along microtubules as a control mechanism for polymerization and depolymerization processes

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Chinese Physics B 2014年第9期23卷 556-570页

作者： L.Kavitha A.Muniyappan S.Zdravkovi M.V.Satari A.Marlewski S.Dhamayanthi D.Gopi Department of Physics School of Basic and Applied SciencesCentral University of Tamilnadu (CUTN) The Abdus Salam International Center for Theoretical Physics Department of Physics Periyar University Institut za nuklearne nauke Vinca Laboratorija za atomsku fiziku 040Univerzitet u Beogradu Fakultet tehnickih nauka Univerzitet u Novom Sadu Institute of Mathematics Poznan University of Technology Center for Nanoscience and Nanotechnology Periyar University Department of Chemistry Periyar University

Among many types of proteinaceous filaments, microtubules （MTs） constitute the most rigid components of the cellular cytoskeleton. Microtubule dynamics is essential for many vital cellular processes such as intracellular transport, metabolism, and cell division. We investigate the nonlinear dynamics of inhomogeneous microtubulin systems and the MT dynamics is found to be governed by a perturbed sine-Gordon equation. In the presence of various competing nonlinear inhomogeneities, it is shown that this nonlinear model can lead to the existence of kink and antikink solitons moving along MTs. We demonstrate kink-antikink pair collision in the framework of Hirota＇s bilinearization method. We conjecture that the collisions of the quanta of energy propagating in the form of kinks and antikinks may offer a new view of the mechanism of the retrograde and anterograde transport direction regulation of motor proteins in microtubulin systems.

关键词： microtubules solitons solitary solutions partial differential equations

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Employment of Jacobian elliptic functions for solving problems in nonlinear dynamics of microtubules

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Chinese Physics B 2014年第2期23卷 178-182页

作者： Slobodan Zekovi Annamalai Muniyappan Slobodan Zdravkovi Louis Kavitha Institut za nuklearne nauke Vina Laboratorija za atomsku fiziku 040Univerzitet u Beogradu Department of Physics Periyar University Center for Nanoscience and Nanotechnology Periyar University

We show how Jacobian elliptic functions （JEFs） can be used to solve ordinary differential equations （ODEs） describing the nonlinear dynamics of microtubules （MTs）. We demonstrate that only one of the JEFs can be used while the remaining two do not represent the solutions of the crucial differential equation. We show that a kinkbtype soliton moves along MTs. Besides this solution, we also discuss a few more solutions that may or may not have physical meanings. Finally, we show what kind of ODE can be solved by using JEFs.

关键词： Jacobian elliptic functions ordinary differential equations microtubules kink soliton

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Preparation and magnetic properties of Fe_2O_3 microtubules prepared by sol-gel template method

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Rare Metals 2010年第5期29卷 501-504页

作者： CHANG Chuanbo ZHANG Cunrui WANG Wenyan LI Qiaoling Department of Chemistry North University of China Taiyuan 030051 China School of Chemical Engineering andEnvironment North University of China Taiyuan 030051 China

Fe（OH）3 precursor sol was prepared by a sol-gel method. The precursor sol was dipped onto the absorbent cotton, and gel was formed on the absorbent cotton template after the volatilization of moisture. Fe2O3 microtubules were synthesized after the process of self-propagation or calcination. The phase, morphology, and particle diameter of the samples were examined by X-ray diffraction （XRD） and scanning electron microscopy （SEM）, and the magnetic properties of the samples were measured using a vibrating sample magnetometer （VSM）. The external diameters of Fe2O3 microtubules ranged between 8 and 13 μm, and the wall thicknesses ranged between 0.5 and 2 μm. The type of the calcination method plays a significant role in developing the Fe2O3 phase and the variation in the magnetic properties in the sol-gel template complexing method. γ-Fe2O3 was synthesized by a self-propagation method. However, α-Fe203 was synthesized after calcination at 400℃ for 2 h. The coercivity of the samples synthesized by calcination at 400℃ for 2 h after self-propagation was found to increase significantly, thereby presenting hard magnetic properties.

关键词： inorganic compounds iron oxides microtubules sol-gel process magnetic properties

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Quantitative analysis of taxane drug target engagement of microtubules in circulating tumor cells from metastatic castration resistant prostate cancer patients treated with CRXL301,a nanoparticle of docetaxel

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Cancer Drug Resistance 2020年第3期3卷 636-646页

作者： Eiman Mukhtar Daniel Worroll Giuseppe Galletti Shelly Schuster Sarina A.Piha-Paul Paraskevi Giannakakou Department of Medicine Hematology/OncologyWeill Cornell MedicineNew YorkNY 10065USA. Sandra and Edward Meyer Cancer Center Department of MedicineWeill Cornell MedicineNew YorkNY 10065USA. NewLink Genetics Corporation AmesIA 50010USA. The University of Texas MD Anderson Cancer CenterHoustonTX 77030USA.

Aim:We reviewed the radiographic response of three patients with metastatic castration-resistant prostate cancer treated with CRXL301,a docetaxel nanoparticle.For these three patients,we isolated and analyzed circulating tumor cells(CTCs)to explore microtubule(MT)drug-target engagement(MT-DTE)as a biomarker of response to treatment.MT-DTE was based on a quantitative assessment of the MT cytoskeleton in CTCs from pre-and posttreatment patient samples as a potential read-out of CRXL301 activity.Methods:We isolated CTCs using negative CD45+depletion and subjected them to multiplex confocal microscopy using our established protocol.CTCs were identified as CD45-/CK+/DAPI+cells and MT-DTE was determined using our developed imaging algorithm.We quantified MT bundling in CTCs across multiple time points,from baseline to on-treatment to disease progression.Here,we describe the longitudinal analysis of MT-DTE in CTCs from patients treated with CRXL301 and its correlation with response to treatment.Results:We collected CTCs at seven time points from three metastatic castration-resistant prostate cancer patients.Clinical response was evaluated by Response Evaluation Criteria in Solid Tumors(RECIST)v.1.1 criteria in those patients with measurable disease.Of the three patients enrolled,one experienced partial response(-50%)to CRXL301 and two patients were unevaluable given bone only disease.Notably,however,these two patients showed stable disease clinically based on bone scans.MT-DTE across all time points revealed that,early time points within four and 24 h of drug administration exhibited the highest levels of drug engagement(MT-DTE)as compared to baseline.However,these early time points did not correlate with clinical response.We observed that the CTCs collected one week after the first or second dose of CRXL301 treatment in the responding patient had numerically higher levels of MT-DTE as compared to the other two patients.Conclusion:Taxane on-target activity can be detected and analyzed quantitatively in CTCs by tubulin i

关键词： Liquid biopsy circulating tumor cells castration-resistant prostate cancer microtubules taxanes biomarkers

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Organizing and Disorganizing Resonances of microtubules, Stem Cells, and Proteins Calculated by a Quantum Equation of Coherence

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Journal of Modern Physics 2022年第12期13卷 1530-1580页

作者： Hans J. H. Geesink Marcus Schmieke DSM-Research Geleen Netherlands Institute of Existential Consciousness Research (ECR) Berlin Germany Dev Sanskriti University Haridwar India

Conformational states of microtubules and proteins have typical spatial-spectral arrangements of atoms, called spatial coherence, that are characteristic for building, homeostasis, decay, and apoptosis. microtubules show a principle of a self-organizing-synergetic structure called a Fröhlich-Bose-Einstein state. The spatial coherence of this state can be described by a toroidal quantum equation of coherence. In this space, microtubules and proteins have typical discrete frequency patterns. These frequencies comply with two proposed quantum wave equations of respective coherence (regulation) and decoherence (deregulation), that describe quantum entangled and disentangled states. The proposed equation of coherence shows the following typical scale invariant distribution of energy: En = ħωref 2q3m. The proposed model supports quantum entanglement and is in line with the earlier published models of Fröhlich, Davydov, and Chern. A meta-analysis shows a semi-harmonic scale-invariant pattern for microtubules, stem cells, proteins, and EEG- and MEG-patterns. A fit has been found for about 50 different organizing frequencies and 5 disorganizing frequencies of measured microtubule frequencies that fit with the calculated values of the proposed quantum equations, which are positioned in a nested toroidal geometry. All measured and analysed frequencies of microtubules comply with the same energy distribution found for Bose-Einstein condensates. The overall results show a presence of an informational quantum code, a direct relation with the eigenfrequencies of microtubules, stem cells, DNA, and proteins, that supplies information to realize biological order in life cells and substantiates a collective Fröhlich-Bose-Einstein type of behaviour and further support the models of Tuszynski, Hameroff, Bandyopadhyay, Del Giudice and Vitiello, Katona, Pettini, and Pokorny.

关键词： Quantum Coherence Coherence and Decoherence Electromagnetic Frequencies Quantum Biology Quantum Wave Equation Fröhlich microtubules Proteins Healthy and Unhealthy Frequency Patterns

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