2025
Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo
Hernandez B, Tetlak P, Domingo-Muelas A, Akizawa H, Skory R, Ardestani G, Biro M, Liu X, Bissiere S, Sakkas D, Plachta N. Actin organizes chromosomes and microtubules to ensure mitotic fidelity in the preimplantation embryo. Science 2025, 388: eads1234. PMID: 40403077, DOI: 10.1126/science.ads1234.Peer-Reviewed Original ResearchConceptsMitotic fidelityError-free chromosome segregationBranched actin filamentsPreimplantation embryosNuclear envelope breakdownRounds of cell divisionNuclear actinFilament disassemblyActin cablesActin filamentsChromosome segregationNuclear peripherySpindle elongationMammalian developmentCell divisionProphase chromosomesSpindle assembly mechanismsEnvelope breakdownAssembly mechanismsGenetic materialActinChromosomeMammalian embryosMouse embryosHuman embryosVimentin filament transport and organization revealed by single-particle tracking and 3D FIB-SEM
Renganathan B, Moore A, Yeo W, Petruncio A, Ackerman D, Weigel A, Team T, Pasolli H, Xu C, Shtengel G, Hess H, Serpinskaya A, Zhang H, Lippincott-Schwartz J, Gelfand V. Vimentin filament transport and organization revealed by single-particle tracking and 3D FIB-SEM. Journal Of Cell Biology 2025, 224: e202406054. PMID: 40062969, PMCID: PMC11893169, DOI: 10.1083/jcb.202406054.Peer-Reviewed Original Research
2024
Phase separation of microtubule-binding proteins - implications for neuronal function and disease.
Duan D, Koleske A. Phase separation of microtubule-binding proteins - implications for neuronal function and disease. Journal Of Cell Science 2024, 137 PMID: 39679446, PMCID: PMC11795294, DOI: 10.1242/jcs.263470.Peer-Reviewed Original ResearchConceptsMT-binding proteinsLiquid-liquid phase separationRegulation of MT dynamicsProtein liquid-liquid phase separationNeuronal developmentTau neurofibrillary tanglesCytoskeletal regulationMT dynamicsNeurofibrillary tanglesBinding domainMT nucleationBiological functionsDisordered regionsAlzheimer's diseaseNeurodegenerative diseasesIn vivo studiesMaintains homeostasisMicrotubulesNeuronal functionMature neuronsProteinRegulationIn vitroFormation of aggregatesIn vitro studiesAurora B controls anaphase onset and error-free chromosome segregation in trypanosomes
Ballmer D, Lou H, Ishii M, Turk B, Akiyoshi B. Aurora B controls anaphase onset and error-free chromosome segregation in trypanosomes. Journal Of Cell Biology 2024, 223: e202401169. PMID: 39196069, PMCID: PMC11354203, DOI: 10.1083/jcb.202401169.Peer-Reviewed Original ResearchConceptsAurora BAnaphase onsetMetaphase-to-anaphase transitionPromote mitotic exitComplex regulatory circuitryEarly-branching eukaryotesKinetochore-microtubule attachmentsAurora B activityDelays anaphase onsetAurora B kinaseCell cycle progressionSpindle assembly checkpointKinetochore proteinsMitotic exitOuter kinetochoreChromosome segregationChromosome missegregationRegulatory circuitrySpindle microtubulesAurora B inhibitionCycle progressionTrypanosoma bruceiAssembly checkpointB kinaseKinetochorePathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics
DeSpenza T, Singh A, Allington G, Zhao S, Lee J, Kiziltug E, Prina M, Desmet N, Dang H, Fields J, Nelson-Williams C, Zhang J, Mekbib K, Dennis E, Mehta N, Duy P, Shimelis H, Walsh L, Marlier A, Deniz E, Lake E, Constable R, Hoffman E, Lifton R, Gulledge A, Fiering S, Moreno-De-Luca A, Haider S, Alper S, Jin S, Kahle K, Luikart B. Pathogenic variants in autism gene KATNAL2 cause hydrocephalus and disrupt neuronal connectivity by impairing ciliary microtubule dynamics. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2314702121. PMID: 38916997, PMCID: PMC11228466, DOI: 10.1073/pnas.2314702121.Peer-Reviewed Original ResearchConceptsCongenital hydrocephalusCerebral ventriculomegalyPathogenic variantsPrefrontal pyramidal neuronsGenetic subsets of patientsDevelopment of ventriculomegalyRadial gliaSubsets of patientsHigh-frequency firingNeuronal connectivityHeterozygous germline variantsAutism spectrum disorderVentricular-subventricular zoneMicrotubule dynamicsImpaired spermatogenesisCSF shuntingExcitatory driveMicrotubule-severing ATPasePyramidal neuronsDisrupt neuronal connectivityGermline variantsVentriculomegalyCSF homeostasisDisrupt microtubule dynamicsPlanar cell polarityMicrotubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy
Danziger M, Noble H, Roque D, Xu F, Rao G, Santin A. Microtubule-Targeting Agents: Disruption of the Cellular Cytoskeleton as a Backbone of Ovarian Cancer Therapy. Advances In Experimental Medicine And Biology 2024, 1452: 1-19. PMID: 38805122, DOI: 10.1007/978-3-031-58311-7_1.Peer-Reviewed Original ResearchConceptsOvarian cancer therapyCancer therapyTargets of anti-cancer therapyIntracellular traffickingCellular processesCellular cytoskeletonMicrotubule-active agentsAnti-cancer therapyMicrotubule-stabilizing agentEffective regimenDynamic polymersDevelopment of resistanceB-tubulinTherapeutic challengeMicrotubulesRecurrent settingTherapyEukaryotesCytoskeletonMitosisHeterodimerMotilityTraffickingRegimensReplicationNoncanonical interaction with microtubules via the N-terminal nonmotor domain is critical for the functions of a bidirectional kinesin
Singh S, Siegler N, Pandey H, Yanir N, Popov M, Goldstein-Levitin A, Sadan M, Debs G, Zarivach R, Frank G, Kass I, Sindelar C, Zalk R, Gheber L. Noncanonical interaction with microtubules via the N-terminal nonmotor domain is critical for the functions of a bidirectional kinesin. Science Advances 2024, 10: eadi1367. PMID: 38324691, PMCID: PMC10849588, DOI: 10.1126/sciadv.adi1367.Peer-Reviewed Original ResearchMeSH KeywordsCryoelectron MicroscopyKinesinsMicrotubulesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsBidirectional motilityKinesin-5Plus-end-directed motilityKinesin-5 motorsCryo-EMC-terminal tailCryo-EM mapsPlus-end-directed kinesinCryo-electron microscopyDeletion mutantsNoncanonical interactionsIntracellular functionsCin8Cryo-electronMotor domainMotilityNonmotor domainsMutantsB-tubulinSingle-moleculeCell viabilityIn vivoIn vitroIn vitro experimentsLocal defects
2023
Dynamic regulation of LINC complex composition and function across tissues and contexts
King M. Dynamic regulation of LINC complex composition and function across tissues and contexts. FEBS Letters 2023, 597: 2823-2832. PMID: 37846646, DOI: 10.1002/1873-3468.14757.Peer-Reviewed Original ResearchMeSH KeywordsCell NucleusCytoskeletonMechanotransduction, CellularMicrotubulesNuclear EnvelopeNuclear MatrixConceptsLINC complex componentsLINC complexLinker of nucleoskeletonProtein turnover mechanismsCytoplasmic intermediate filament networkIntermediate filament networkCytoskeleton (LINC) complexComplex componentsNuclear laminaCellular contextCytoplasmic cytoskeletonCell biologistsDynamic regulationNuclear envelopeRegulated expressionTurnover mechanismsFilament networkSplice variantsCell typesProtein configurationUnique functionCytoskeletonConcept of mechanotransductionComplexesNucleoskeletonAbl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation
Duan D, Lyu W, Chai P, Ma S, Wu K, Wu C, Xiong Y, Sestan N, Zhang K, Koleske A. Abl2 repairs microtubules and phase separates with tubulin to promote microtubule nucleation. Current Biology 2023, 33: 4582-4598.e10. PMID: 37858340, PMCID: PMC10877310, DOI: 10.1016/j.cub.2023.09.018.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell MovementChlorocebus aethiopsCOS CellsMicrotubule-Associated ProteinsMicrotubulesTubulinConceptsCOS-7 cellsMT nucleationMT latticeFamily kinasesTubulin recruitmentLiquid-liquid phase separationTubulin C-terminal tailsCryo-EM analysisC-terminal tailAbl family kinasesWild-type cellsC-terminal halfRescue frequencyGenetic experimentsNeuronal morphogenesisMicrotubule nucleationSplice isoformsMicrotubule dynamicsNocodazole treatmentMolecular mechanismsAxon guidanceCell migrationDamage sitesABL2MT assemblySPAK-dependent cotransporter activity mediates capillary adhesion and pressure during glioblastoma migration in confined spaces.
Lee S, Yousafzai M, Mohler K, Yadav V, Amiri S, Szuszkiewicz J, Levchenko A, Rinehart J, Murrell M. SPAK-dependent cotransporter activity mediates capillary adhesion and pressure during glioblastoma migration in confined spaces. Molecular Biology Of The Cell 2023, 34: ar122. PMID: 37672340, PMCID: PMC10846615, DOI: 10.1091/mbc.e23-03-0103.Peer-Reviewed Original ResearchMicrotubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport
Ton W, Wang Y, Chai P, Beauchamp-Perez C, Flint N, Lammers L, Xiong H, Zhang K, Markus S. Microtubule-binding-induced allostery triggers LIS1 dissociation from dynein prior to cargo transport. Nature Structural & Molecular Biology 2023, 30: 1365-1379. PMID: 37322240, PMCID: PMC10590275, DOI: 10.1038/s41594-023-01010-x.Peer-Reviewed Original ResearchMeSH KeywordsDyneinsHumansMicrotubule-Associated ProteinsMicrotubulesProtein BindingSaccharomyces cerevisiaeConceptsCryo-EM structureCargo transportProtein Lis1Human dyneinDynein mutantsCytoplasmic dyneinStructural insightsDynein activityIntracellular localizationCritical regulatorDynein activationLIS1Conformational changesDyneinMotor domainMutantsBindingHigh affinityAffinityYeastMicrotubulesRegulatorRegulationTransportActivationActin limits egg aneuploidies associated with female reproductive aging
Dunkley S, Mogessie B. Actin limits egg aneuploidies associated with female reproductive aging. Science Advances 2023, 9: eadc9161. PMID: 36662854, PMCID: PMC9858517, DOI: 10.1126/sciadv.adc9161.Peer-Reviewed Original ResearchDynamic microtubules slow down during their shrinkage phase
Luchniak A, Kuo Y, McGuinness C, Sutradhar S, Orbach R, Mahamdeh M, Howard J. Dynamic microtubules slow down during their shrinkage phase. Biophysical Journal 2023, 122: 616-623. PMID: 36659852, PMCID: PMC9989939, DOI: 10.1016/j.bpj.2023.01.020.Peer-Reviewed Original ResearchHigh-Resolution Structural Analysis of Dyneins by Cryo-electron Microscopy
Chai P, Rao Q, Wang Y, Zhang K. High-Resolution Structural Analysis of Dyneins by Cryo-electron Microscopy. Methods In Molecular Biology 2023, 2623: 257-279. PMID: 36602691, PMCID: PMC10371436, DOI: 10.1007/978-1-0716-2958-1_16.ChaptersConceptsCryo-electron microscopyHigh-resolution structural informationLarge molecular machineHigh-resolution structuresCryo-EM approachResolution structural analysisProtein complexesStructural biologistsCellular cargoMolecular machinesDyneinDepth mechanistic understandingMolecular motorsMechanistic understandingCiliary motilityFlexible conformationIntricate architectureStructural informationMacromolecular structureForce generatorStructural analysisBiologistsSimilar structureCargoMicroscopyCLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner
Luo W, Demidov V, Shen Q, Girão H, Chakraborty M, Maiorov A, Ataullakhanov F, Lin C, Maiato H, Grishchuk E. CLASP2 recognizes tubulins exposed at the microtubule plus-end in a nucleotide state–sensitive manner. Science Advances 2023, 9: eabq5404. PMID: 36598991, PMCID: PMC9812398, DOI: 10.1126/sciadv.abq5404.Peer-Reviewed Original Research
2022
Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion
Huet-Calderwood C, Rivera-Molina F, Toomre D, Calderwood D. Fibroblasts secrete fibronectin under lamellipodia in a microtubule- and myosin II–dependent fashion. Journal Of Cell Biology 2022, 222: e202204100. PMID: 36416725, PMCID: PMC9699186, DOI: 10.1083/jcb.202204100.Peer-Reviewed Original ResearchConceptsFN secretionFocal adhesion dynamicsExtracellular matrixFocal adhesion formationSites of exocytosisLive-cell microscopyIntegrin-independent mannerCytoskeletal dynamicsFocal adhesionsAdhesion dynamicsRegulatory componentsMyosin IIIntact microtubulesCell polarizationCell adhesionIntegrin receptorsFN depositionLamellipodiaMicrotubulesFibronectinAdhesion formationNew adhesion formationFibroblastsII-dependent fashionCellsMulti-curve fitting and tubulin-lattice signal removal for structure determination of large microtubule-based motors
Chai P, Rao Q, Zhang K. Multi-curve fitting and tubulin-lattice signal removal for structure determination of large microtubule-based motors. Journal Of Structural Biology 2022, 214: 107897. PMID: 36089228, PMCID: PMC10321216, DOI: 10.1016/j.jsb.2022.107897.Peer-Reviewed Original ResearchThe need for speed: Migratory cells in tight spaces boost their molecular clock
Bhaskar D, Hruska AM, Wong IY. The need for speed: Migratory cells in tight spaces boost their molecular clock. Cell Systems 2022, 13: 509-511. PMID: 35863324, PMCID: PMC10071288, DOI: 10.1016/j.cels.2022.06.002.Peer-Reviewed Original ResearchThe force required to remove tubulin from the microtubule lattice by pulling on its α-tubulin C-terminal tail
Kuo YW, Mahamdeh M, Tuna Y, Howard J. The force required to remove tubulin from the microtubule lattice by pulling on its α-tubulin C-terminal tail. Nature Communications 2022, 13: 3651. PMID: 35752623, PMCID: PMC9233703, DOI: 10.1038/s41467-022-31069-x.Peer-Reviewed Original ResearchA molecular clock controls periodically driven cell migration in confined spaces
Lee SH, Hou JC, Hamidzadeh A, Yousafzai MS, Ajeti V, Chang H, Odde DJ, Murrell M, Levchenko A. A molecular clock controls periodically driven cell migration in confined spaces. Cell Systems 2022, 13: 514-529.e10. PMID: 35679858, DOI: 10.1016/j.cels.2022.05.005.Peer-Reviewed Original ResearchConceptsCell migrationSmall GTPase RhoAFaster cell migrationNegative feedback loopExchange factorMolecular clockGEF-H1RhoA guanineGTPase RhoAMicrotubule dynamicsMolecular mechanismsClock controlCell spreadExtracellular matrixIntracellular CaTissue reorganizationFeedback loopMigrationRhoAAbundanceGuanineBetter understanding
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