2023
Dynamic 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 Research
2022
The 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 ResearchCounting fluorescently labeled proteins in tissues in the spinning–disk microscope using single–molecule calibrations
Liao M, Kuo Y, Howard J. Counting fluorescently labeled proteins in tissues in the spinning–disk microscope using single–molecule calibrations. Molecular Biology Of The Cell 2022, 33: ar48. PMID: 35323029, PMCID: PMC9265152, DOI: 10.1091/mbc.e21-12-0618.Peer-Reviewed Original ResearchConceptsEnd-binding protein 1Spinning-disk confocal microscopyConfocal microscopySingle-molecule imagingComplex biological phenomenaFly larvaeLiving cellsCell surfaceMicrotubule endsBiological phenomenaProtein 1Brightness of fluorophoresCytoplasmic concentrationEpifluorescence microscopeBiological systemsSensory neuronsCellsSingle moleculesAbsolute numberMolecular numberTissueLarvaeMicrotubulesEGFPProtein
2021
Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism
Rao Q, Han L, Wang Y, Chai P, Kuo YW, Yang R, Hu F, Yang Y, Howard J, Zhang K. Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism. Nature Structural & Molecular Biology 2021, 28: 799-810. PMID: 34556869, PMCID: PMC8500839, DOI: 10.1038/s41594-021-00656-9.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCryoelectron MicroscopyDyneinsMicrotubulesModels, MolecularTetrahymena thermophilaConceptsOuter arm dyneinMicrotubule doubletsDistinct microtubule-binding domainsHigh-resolution structuresAction of dyneinsMicrotubule-binding domainNative tracksATP hydrolysisDynein motorsHydrolyze ATPConformational changesNucleotide cycleMotor coordination mechanismATP turnoverDyneinHead interactionsMechanical forces
2020
Cutting, Amplifying, and Aligning Microtubules with Severing Enzymes
Kuo YW, Howard J. Cutting, Amplifying, and Aligning Microtubules with Severing Enzymes. Trends In Cell Biology 2020, 31: 50-61. PMID: 33183955, PMCID: PMC7749064, DOI: 10.1016/j.tcb.2020.10.004.Peer-Reviewed Original ResearchConceptsAAA ATPasesTissue morphogenesisCellular processesMicrotubule cytoskeletonCell divisionGrowth promotionBiophysical advancesSevering enzymesMicrotubule networkMolecular mechanismsStrong promoterMicrotubule growthNeuronal developmentShort filamentsMicrotubulesSpastinEnzymeSeveringFidgetinKataninCytoskeletonMorphogenesisPromoterProteinRecent work
2019
Spastin is a dual-function enzyme that severs microtubules and promotes their regrowth to increase the number and mass of microtubules
Kuo YW, Trottier O, Mahamdeh M, Howard J. Spastin is a dual-function enzyme that severs microtubules and promotes their regrowth to increase the number and mass of microtubules. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 5533-5541. PMID: 30837315, PMCID: PMC6431158, DOI: 10.1073/pnas.1818824116.Peer-Reviewed Original ResearchConceptsDual-function enzymeMicrotubule dynamicsMass of microtubulesMicrotubule cytoskeletonDynamic cellular processesCellular processesMicrotubule regrowthNeuronal morphogenesisSevering activityVivo phenotypeMicrotubule assaysMicrotubulesNumber of microtubulesSpastinMicrotubule fragmentsRescue frequencyShort fragmentsCytoskeletonMicrotubule massObserved exponential increaseEnzymeRemodelersFidgetinKataninCiliogenesis
2018
Label‐free high‐speed wide‐field imaging of single microtubules using interference reflection microscopy
MAHAMDEH M, SIMMERT S, LUCHNIAK A, SCHÄFFER E, HOWARD J. Label‐free high‐speed wide‐field imaging of single microtubules using interference reflection microscopy. Journal Of Microscopy 2018, 272: 60-66. PMID: 30044498, PMCID: PMC6486835, DOI: 10.1111/jmi.12744.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCattleFluorescenceLightMicroscopy, FluorescenceMicroscopy, InterferenceMicrotubulesConceptsDifferential interference contrastReflection microscopyInterference contrastCostly optical componentsWide-field imagingLabel-free imagingHollow cylindrical beamsDark-field condenserInterference contrast imagesDifferential interference contrast (DIC) imagesEfficient fluorescent labelingOptical componentsInterference reflection microscopyOptical misalignmentMicroscope modificationsProtein building blocksNomarski prismOptical qualityHigh-speed imagingNumber of drawbacksFree imagingLight interferenceCylindrical beamsContrast imagesHigh contrast
2008
XMAP215 Is a Processive Microtubule Polymerase
Brouhard GJ, Stear JH, Noetzel TL, Al-Bassam J, Kinoshita K, Harrison SC, Howard J, Hyman AA. XMAP215 Is a Processive Microtubule Polymerase. Cell 2008, 132: 79-88. PMID: 18191222, PMCID: PMC2311386, DOI: 10.1016/j.cell.2007.11.043.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesBiological AssayCatalytic DomainCell DifferentiationCell EnlargementCell LineCytoskeletonDiffusionDimerizationFetal ProteinsForminsGreen Fluorescent ProteinsMicrofilament ProteinsMicroscopy, FluorescenceMicrotubule-Associated ProteinsMicrotubulesNuclear ProteinsPolymersProtein BindingProtein Structure, TertiaryProtein TransportSpodopteraSus scrofaTubulinXenopus laevisXenopus ProteinsConceptsFamily of proteinsSingle-molecule assaysActin polymerasesMicrotubule cytoskeletonProcessive polymeraseTubulin subunit additionDynamic microtubulesMicrotubule polymeraseMicrotubule growthCytoskeletal polymersXMAP215Plus endsMicrotubule latticePolymeraseSubunit additionCell proliferationFree tubulinTubulin dimersMicrotubulesCommon mechanismFast growthTip trackingGrowthCytoskeletonRapid assembly
2006
Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner
Varga V, Helenius J, Tanaka K, Hyman AA, Tanaka TU, Howard J. Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner. Nature Cell Biology 2006, 8: 957-962. PMID: 16906145, DOI: 10.1038/ncb1462.Peer-Reviewed Original ResearchConceptsKinesin-8 proteinsLength-dependent depolymerizationYeast kinesin-8Length-dependent mannerMetazoan cellsMicrotubule cytoskeletonMitotic spindleDisassemble microtubulesSpindle lengthKinesin-8Kinesin-13Kip3pPlus endsMicrotubulesConstituent microtubulesLong microtubulesNew mechanismCytoskeletonFungiKinesinProteinSpindleCellsThe depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends
Helenius J, Brouhard G, Kalaidzidis Y, Diez S, Howard J. The depolymerizing kinesin MCAK uses lattice diffusion to rapidly target microtubule ends. Nature 2006, 441: 115-119. PMID: 16672973, DOI: 10.1038/nature04736.Peer-Reviewed Original Research
1994
The force exerted by a single kinesin molecule against a viscous load
Hunt AJ, Gittes F, Howard J. The force exerted by a single kinesin molecule against a viscous load. Biophysical Journal 1994, 67: 766-781. PMID: 7948690, PMCID: PMC1225420, DOI: 10.1016/s0006-3495(94)80537-5.Peer-Reviewed Original Research
1993
Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape.
Gittes F, Mickey B, Nettleton J, Howard J. Flexural rigidity of microtubules and actin filaments measured from thermal fluctuations in shape. Journal Of Cell Biology 1993, 120: 923-934. PMID: 8432732, PMCID: PMC2200075, DOI: 10.1083/jcb.120.4.923.Peer-Reviewed Original Research