2024
Channel width modulates the permeability of DNA origami–based nuclear pore mimics
Feng Q, Saladin M, Wu C, Cao E, Zheng W, Zhang A, Bhardwaj P, Li X, Shen Q, Kapinos L, Kozai T, Mariappan M, Lusk C, Xiong Y, Lim R, Lin C. Channel width modulates the permeability of DNA origami–based nuclear pore mimics. Science Advances 2024, 10: eadq8773. PMID: 39536094, PMCID: PMC11559598, DOI: 10.1126/sciadv.adq8773.Peer-Reviewed Original ResearchA-tisket, a-tasket, what a beautiful nuclear basket
Lusk C, King M. A-tisket, a-tasket, what a beautiful nuclear basket. Cell 2024, 187: 5225-5227. PMID: 39303690, DOI: 10.1016/j.cell.2024.08.030.Peer-Reviewed Original Research
2023
An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity
Ader N, Chen L, Surovtsev I, Chadwick W, Rodriguez E, King M, Lusk C. An ESCRT grommet cooperates with a diffusion barrier to maintain nuclear integrity. Nature Cell Biology 2023, 25: 1465-1477. PMID: 37783794, PMCID: PMC11365527, DOI: 10.1038/s41556-023-01235-4.Peer-Reviewed Original ResearchMeSH KeywordsAnaphaseEndosomal Sorting Complexes Required for TransportNuclear EnvelopeNuclear PoreSchizosaccharomycesConceptsSpindle pole body proteinNuclear envelope barrierESCRT-III proteinsNuclear pore complexSpindle pole bodyNucleocytoplasmic compartmentalizationESCRT functionPore complexPole bodyDistinct complementNuclear compartmentNuclear integrityTransport proteinsMolecular mechanismsRemodelling mechanismProteinBody proteinChanging the guard—nuclear pore complex quality control
Veldsink A, Gallardo P, Lusk C, Veenhoff L. Changing the guard—nuclear pore complex quality control. FEBS Letters 2023, 597: 2739-2749. PMID: 37715940, DOI: 10.1002/1873-3468.14739.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusNuclear EnvelopeNuclear PoreNuclear Pore Complex ProteinsThe capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores
Shen Q, Kumari S, Xu C, Jang S, Shi J, Burdick R, Levintov L, Xiong Q, Wu C, Devarkar S, Tian T, Tripler T, Hu Y, Yuan S, Temple J, Feng Q, Lusk C, Aiken C, Engelman A, Perilla J, Pathak V, Lin C, Xiong Y. The capsid lattice engages a bipartite NUP153 motif to mediate nuclear entry of HIV-1 cores. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2202815120. PMID: 36943880, PMCID: PMC10068764, DOI: 10.1073/pnas.2202815120.Peer-Reviewed Original ResearchConceptsHIV-1 capsidC-terminal tail regionTriple arginine motifNuclear pore complexPhenylalanine-glycine motifsBipartite motifNuclear importPore complexNuclear poresNuclear entryNup153Capsid latticeInteraction moduleProtein latticeCA assemblyCA hexamersIntact capsidsNucleoporinsHIV-1 coreMotifCapsidTail regionIntact formInfection studiesMechanistic evidenceModeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels
Shen Q, Feng Q, Wu C, Xiong Q, Tian T, Yuan S, Shi J, Bedwell G, Yang R, Aiken C, Engelman A, Lusk C, Lin C, Xiong Y. Modeling HIV-1 nuclear entry with nucleoporin-gated DNA-origami channels. Nature Structural & Molecular Biology 2023, 30: 425-435. PMID: 36807645, PMCID: PMC10121901, DOI: 10.1038/s41594-023-00925-9.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusCapsid ProteinsCell LineDNAHIV-1HumansNuclear PoreNuclear Pore Complex ProteinsConceptsNuclear pore complexHIV-1 nuclear entryNuclear entryNuclear importNPC central channelPore complexHost nucleusCapsid dockingVirus genomeAffinity gradientNup153Central channelMechanistic insightsMolecular interactionsCapsidNucleoporinsNup358Nup62GenomeNucleusVirusDockingVirus-1 infectionImportComplexes
2022
Quality control mechanisms that protect nuclear envelope identity and function
Mannino PJ, Lusk CP. Quality control mechanisms that protect nuclear envelope identity and function. Journal Of Cell Biology 2022, 221: e202205123. PMID: 36036741, PMCID: PMC9442147, DOI: 10.1083/jcb.202205123.Peer-Reviewed Original ResearchMeSH KeywordsEndoplasmic ReticulumNuclear EnvelopeNuclear PoreNuclear Pore Complex ProteinsUbiquitinConceptsNuclear pore complexQuality control mechanismsNuclear envelopeCellular degradative machineryNE integrityGenome stabilityPore complexMembrane remodelingDegradative machineryOuter membraneDistinct biochemistryBiochemical identityEndoplasmic reticulumAutophagy mechanismControl mechanismsSelective barrierPore membraneMembraneRecent workEukaryotesProteomeDeleterious effectsSpecializationMechanismMachinery
2021
Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS
Coyne AN, Baskerville V, Zaepfel BL, Dickson DW, Rigo F, Bennett F, Lusk CP, Rothstein JD. Nuclear accumulation of CHMP7 initiates nuclear pore complex injury and subsequent TDP-43 dysfunction in sporadic and familial ALS. Science Translational Medicine 2021, 13 PMID: 34321318, PMCID: PMC9022198, DOI: 10.1126/scitranslmed.abe1923.Peer-Reviewed Original ResearchConceptsTDP-43 dysfunctionSporadic ALSGlutamate-induced neuronal deathHuman motor cortexAmyotrophic lateral sclerosis/frontotemporal dementiaSpinal neuronsComplex injuriesMotor cortexNeuronal deathFamilial ALSHuman neuronsPathological mechanismsTherapeutic targetFrontotemporal dementiaMRNA expressionNeurodegenerative diseasesDysfunctionGenetic formsCritical mediatorALSNeuronsStem cellsAlterationsPluripotent stem cellsNuclear accumulationDirect binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations
Thaller DJ, Tong D, Marklew CJ, Ader NR, Mannino PJ, Borah S, King MC, Ciani B, Lusk CP. Direct binding of ESCRT protein Chm7 to phosphatidic acid–rich membranes at nuclear envelope herniations. Journal Of Cell Biology 2021, 220: e202004222. PMID: 33464310, PMCID: PMC7816628, DOI: 10.1083/jcb.202004222.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceConserved SequenceEndosomal Sorting Complexes Required for TransportHydrophobic and Hydrophilic InteractionsLipid BilayersModels, BiologicalNuclear EnvelopeNuclear PorePhosphatidic AcidsProtein DomainsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsConceptsNuclear pore complex biogenesisNuclear membrane remodelingNuclear envelope herniationsLAP2-emerinNE remodelingNPC assemblyComplex biogenesisHydrophobic stretchMembrane remodelingChm7Nuclear envelopePA bindingPA metabolismFunctional importanceDirect bindingAmino acidsPhosphatidic acidMembraneBindingHeh1RecruitmentESCRTBiogenesisRemodelingYeast
2019
An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system
Thaller DJ, Allegretti M, Borah S, Ronchi P, Beck M, Lusk CP. An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system. ELife 2019, 8: e45284. PMID: 30942170, PMCID: PMC6461442, DOI: 10.7554/elife.45284.Peer-Reviewed Original ResearchConceptsNuclear pore complexNPC assemblyNuclear membraneNuclear envelope barrierNuclear envelope herniationsNuclear envelope integrityNuclear transport systemXPO1/CRM1Membrane deliveryPore complexEnvelope integrityNuclear transportYeast modelNuclear poresChm7Nuclear envelopeFenestrated sheetHeh1Membrane disruptionMechanical membrane disruptionSelective barrierDisease mechanismsMembrane sealingTransport systemMembrane
2014
Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4
Webster BM, Colombi P, Jäger J, Lusk CP. Surveillance of Nuclear Pore Complex Assembly by ESCRT-III/Vps4. Cell 2014, 159: 388-401. PMID: 25303532, PMCID: PMC4194032, DOI: 10.1016/j.cell.2014.09.012.Peer-Reviewed Original ResearchConceptsNuclear pore complexNPC assemblyNuclear compartmentalizationIntegral inner nuclear membrane proteinsESCRT-III/Vps4Functional nuclear pore complexesNuclear pore complex assemblyInner nuclear membrane proteinPore complex assemblyNuclear membrane proteinsAAA ATPase Vps4LEM familyPore complexAssembly intermediatesMembrane proteinsLoss of compartmentalizationComplex assemblyNuclear envelopeComplex compartmentVps4CompartmentalizationCell functionContinuum of mechanismsAssemblySnf7
2006
Karyopherin-mediated import of integral inner nuclear membrane proteins
King MC, Lusk C, Blobel G. Karyopherin-mediated import of integral inner nuclear membrane proteins. Nature 2006, 442: 1003-1007. PMID: 16929305, DOI: 10.1038/nature05075.Peer-Reviewed Original ResearchConceptsIntegral membrane proteinsInner nuclear membraneINM proteinsMembrane proteinsIntegral inner nuclear membrane proteinsInner nuclear membrane proteinNuclear pore complex proteinsNuclear membrane proteinsRan GTPase cycleBasic sequence motifsNuclear localization signalNuclear pore complexPore complex proteinsAppropriate cellular compartmentDiscrete sequence elementsINM targetingLocalization signalPore complexGTPase cycleNuclear transportSequence motifsCellular compartmentsComplex proteinsSequence elementsKaryopherin β1