2025
The mechanochemical cycle of reactive full-length human dynein 1
Chai P, Yang J, Geohring I, Markus S, Wang Y, Zhang K. The mechanochemical cycle of reactive full-length human dynein 1. Nature Structural & Molecular Biology 2025, 1-13. PMID: 40263469, DOI: 10.1038/s41594-025-01543-3.Peer-Reviewed Original ResearchMechanochemical cycleForce-generating powerstrokeDiverse cellular activitiesDynein's mechanochemical cycleHigh-resolution structuresMicrotubule bindingDynein functionDyneinNucleotide conditionsAdenosine triphosphatase activityCrosstalk mechanismCellular activitiesTriphosphatase activityConformational landscapeMicrotubulesCargo transportComprehensive viewNucleotide
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 studiesViscosity regulates cell spreading and cell‐extracellular matrix interactions
Xiao H, Gong X, Jordan S, Liang Z, Mak M. Viscosity regulates cell spreading and cell‐extracellular matrix interactions. The FEBS Journal 2024, 292: 740-758. PMID: 39529371, PMCID: PMC12002552, DOI: 10.1111/febs.17306.Peer-Reviewed Original ResearchCell spreadingRho-associated protein kinase 1Actin-related protein 2/3Regulation of cell locomotionRegulation of ECM remodelingCollagen substrateRas-related C3 botulinum toxin substrate 1Cell-extracellular matrix interactionsECM remodelingCellular remodelingExtracellular matrixEnhanced cell spreadingProtein kinase 1Membrane rufflingCell locomotionRemodeling of extracellular matrixCellular forcesSubstrate 1Cell migrationCellular spreadingKinase 1Matrix interactionsRac1MicrotubulesRegulationMechanics of spindle orientation in human mitotic cells is determined by pulling forces on astral microtubules and clustering of cortical dynein
Anjur-Dietrich M, Gomez Hererra V, Farhadifar R, Wu H, Merta H, Bahmanyar S, Shelley M, Needleman D. Mechanics of spindle orientation in human mitotic cells is determined by pulling forces on astral microtubules and clustering of cortical dynein. Developmental Cell 2024, 59: 2429-2442.e4. PMID: 38866013, DOI: 10.1016/j.devcel.2024.05.022.Peer-Reviewed Original ResearchMicrotubule-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 settingTherapyEukaryotesCytoskeletonMitosisHeterodimerMotilityTraffickingRegimensReplicationThe physical and cellular mechanism of structural color change in zebrafish
Gur D, Moore A, Deis R, Pang S, Wu X, Pinkas I, Deo C, Iyer N, Hess H, Hammer J, Lippincott-Schwartz J. The physical and cellular mechanism of structural color change in zebrafish. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2308531121. PMID: 38805288, PMCID: PMC11161791, DOI: 10.1073/pnas.2308531121.Peer-Reviewed Original ResearchConceptsMicrotubule organizing centerCellular machineryFluorescence light microscopyOrganizing centerPharmacological perturbationsDyneinIridophoresRegulate body temperatureMicrotubulesCellular mechanismsIntracellular cAMPZebrafishMachineryIntracellular crystalsIon beam scanning electron microscopyGuanine crystalsStructural color changeLight microscopyColor changeUnveiling the secrets of vimentin filament architecture relevant to human disease
Lomakin I, Ho M, Bunick C. Unveiling the secrets of vimentin filament architecture relevant to human disease. Nature Structural & Molecular Biology 2024, 31: 849-851. PMID: 38684931, PMCID: PMC11955283, DOI: 10.1038/s41594-024-01301-x.Peer-Reviewed Original ResearchCollective dynamics of actin and microtubule and its crosstalk mediated by FHDC1
San Tong C, Su M, Sun H, Le Chua X, Xiong D, Guo S, Raj R, Ong N, Lee A, Miao Y, Wu M. Collective dynamics of actin and microtubule and its crosstalk mediated by FHDC1. Frontiers In Cell And Developmental Biology 2024, 11: 1261117. PMID: 38567385, PMCID: PMC10985548, DOI: 10.3389/fcell.2023.1261117.Peer-Reviewed Original ResearchActin wavesActin polymerizationFormin-mediated actin polymerizationDynamics of actinMultiple cellular processesActin nucleationCell cortexCytoskeletal networkCellular processesMicrotubule networkCell divisionMicrotubule depolymerizationActinAntagonistic interplayMicrotubulesMolecular insightsProtein 1CellsCdc42Mast cellsConcurrent releaseDepolymerizationInteractionInhibition
2023
Actin and Microtubules Position Stress Granules
Böddeker T, Rusch A, Leeners K, Murrell M, Dufresne E. Actin and Microtubules Position Stress Granules. PRX Life 2023, 1: 023010. DOI: 10.1103/prxlife.1.023010.Peer-Reviewed Original ResearchNuclear envelope assembly relies on CHMP-7 in the absence of BAF–LEM-mediated hole closure
Barger S, Penfield L, Bahmanyar S. Nuclear envelope assembly relies on CHMP-7 in the absence of BAF–LEM-mediated hole closure. Journal Of Cell Science 2023, 136: jcs261385. PMID: 37795681, PMCID: PMC10668030, DOI: 10.1242/jcs.261385.Peer-Reviewed Original ResearchConceptsNuclear envelope assemblySpindle microtubulesNE assemblyEnvelope assemblyC. elegans oocytesLEM-2C. elegansHelix domainBAF-1Family proteinsNucleoplasmic poolNE formationDistinct rolesMicrotubulesAdditional roleNE stabilityPermeability barrierRedundant mechanismsBAFProteinEmbryo survivalBindingAssemblyElegansAutointegrationMicrotubule-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 ResearchConceptsCryo-EM structureCargo transportProtein Lis1Human dyneinDynein mutantsCytoplasmic dyneinStructural insightsDynein activityIntracellular localizationCritical regulatorDynein activationLIS1Conformational changesDyneinMotor domainMutantsBindingHigh affinityAffinityYeastMicrotubulesRegulatorRegulationTransportActivationLC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy
Omrane M, Ben M'Barek K, Santinho A, Nguyen N, Nag S, Melia T, Thiam A. LC3B is lipidated to large lipid droplets during prolonged starvation for noncanonical autophagy. Developmental Cell 2023, 58: 1266-1281.e7. PMID: 37315562, PMCID: PMC10686041, DOI: 10.1016/j.devcel.2023.05.009.Peer-Reviewed Original ResearchConceptsProtein 1 light chain 3BLarge lipid dropletsLight chain 3BStarvation triggersLipidation reactionNoncanonical autophagyLysosomal pathwayAutophagic processStore lipidsAutophagy mechanismLipid dropletsATG3Large LDsProlonged starvationHuman liver cellsLC3BTimes of scarcityStarvationLiver cellsMacrolipophagyAutophagicClose proximityAutophagyATG5Microtubules
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 fashionCellsCryo-EM structure of an active central apparatus
Han L, Rao Q, Yang R, Wang Y, Chai P, Xiong Y, Zhang K. Cryo-EM structure of an active central apparatus. Nature Structural & Molecular Biology 2022, 29: 472-482. PMID: 35578022, PMCID: PMC9113940, DOI: 10.1038/s41594-022-00769-9.Peer-Reviewed Original ResearchConceptsCentral apparatusDiverse cellular activitiesKinesin-like proteinCryo-EM structureArmadillo repeat proteinsCryo-electron microscopyHigh-resolution structuresEukaryotic speciesProtein subunitsMotile ciliaBridge proteinsPair of microtubulesRegulatory roleCellular activitiesProteinDynamic conformational behaviorCiliary motilityCiliaCiliary beatingStructural frameworkConformational behaviorSubunitsMicrotubulesRegulatorSpeciesCounting 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 numberTissueLarvaeMicrotubulesEGFPProteinKIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization
Zheng R, Du Y, Wang X, Liao T, Zhang Z, Wang N, Li X, Shen Y, Shi L, Luo J, Xia J, Wang Z, Xu J. KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization. ELife 2022, 11: e72483. PMID: 35138249, PMCID: PMC8828051, DOI: 10.7554/elife.72483.Peer-Reviewed Original ResearchConceptsDynamic microtubulesFunctional plasticity of synapsesRegulate synaptic developmentConditional knockout approachFunction of KIF2CNervous systemNeuronal activity-dependent mannerPlasticity of synapsesProtein traffickingActivity-dependent mannerDepolymerizing proteinsRNAi knockdownSynaptic plasticityExpression of AMPA receptorsMicrotubule dynamicsMicrotubule invasionMicrotubule depolymerizationImpaired excitatory transmissionKnockout approachRegulatory mechanismsKIF2CDepolymerization capabilityLong-term potentiationSynaptic developmentMicrotubules
2021
ER-to-Golgi protein delivery through an interwoven, tubular network extending from ER
Weigel AV, Chang CL, Shtengel G, Xu CS, Hoffman DP, Freeman M, Iyer N, Aaron J, Khuon S, Bogovic J, Qiu W, Hess HF, Lippincott-Schwartz J. ER-to-Golgi protein delivery through an interwoven, tubular network extending from ER. Cell 2021, 184: 2412-2429.e16. PMID: 33852913, DOI: 10.1016/j.cell.2021.03.035.Peer-Reviewed Original ResearchConceptsTubular networkEarly secretory compartmentsAccurate traffickingProtein exportDiverse proteinsProtein localizationSecretory pathwayMammalian cellsSecretory compartmentsCargo entryGolgi apparatusLipid bilayersIllumination microscopyBeam scanning electron microscopyIon beam scanning electron microscopyProtein deliveryCOPIIERDynamic 3D viewsTraffickingMicrotubulesProteinVesiclesPathwayCompartments
2020
3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cells
Müller A, Schmidt D, Xu CS, Pang S, D’Costa J, Kretschmar S, Münster C, Kurth T, Jug F, Weigert M, Hess HF, Solimena M. 3D FIB-SEM reconstruction of microtubule–organelle interaction in whole primary mouse β cells. Journal Of Cell Biology 2020, 220: e202010039. PMID: 33326005, PMCID: PMC7748794, DOI: 10.1083/jcb.202010039.Peer-Reviewed Original ResearchConceptsInsulin secretory granulesΒ-cellsSecretory granulesPrimary mammalian cellsFirst 3D reconstructionPrimary mouse β-cellsMouse β-cellsMammalian cellsMicrotubule organizationPlasma membraneIntracellular traffickingIslet β-cellsMicrotubule networkMicrotubulesUnprecedented resolutionCell constituentsMicrotubule numberCell functionGolgi apparatiCentriolesCellsEndocrine cellsGlucose stimulationEndomembranesGranulesPulling the springs of a cell by single-molecule force spectroscopy
Mukherjee C, Bera M, Ainavarapu S, Sengupta K. Pulling the springs of a cell by single-molecule force spectroscopy. Emerging Topics In Life Sciences 2020, 5: 77-87. PMID: 33284963, DOI: 10.1042/etls20200254.Peer-Reviewed Original ResearchConceptsSingle-molecule force spectroscopyFilamentous proteinsForce spectroscopyExtracellular matrix proteinsNucleoskeletal proteinsTraction forceMatrix proteinsNecessary anchorageProteinIntermediate filamentsWhole cellsCurrent understandingTissue repairFundamental unitCellsBiochemical changesFibrillar networkMechanotransductionMicrotubulesMicrofilamentsECMFilamentsRegenerationNucleusCutting, 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
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