2025
The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage
Wang X, Xu P, Bentley-DeSousa A, Hancock-Cerutti W, Cai S, Johnson B, Tonelli F, Shao L, Talaia G, Alessi D, Ferguson S, De Camilli P. The bridge-like lipid transport protein VPS13C/PARK23 mediates ER–lysosome contacts following lysosome damage. Nature Cell Biology 2025, 27: 776-789. PMID: 40211074, PMCID: PMC12081312, DOI: 10.1038/s41556-025-01653-6.Peer-Reviewed Original ResearchConceptsDisease genesResponse to lysosomal damageSurface of lysosomesER–lysosome contactsParkinson's disease genesDelivery to lysosomesLipid transport proteinsLysosomal damageVPS13 proteinsLysosomal surfaceDisease proteinsGenetic studiesDamaged lysosomesVPS13CLysosomal stressLipid transportLysosomesInhibited stateMembrane perturbationRab7Lysosomal dysfunctionProteinVps13LipidGenesMatrix-producing neutrophils populate and shield the skin
Vicanolo T, Özcan A, Li J, Huerta-López C, Ballesteros I, Rubio-Ponce A, Dumitru A, Nicolás-Ávila J, Molina-Moreno M, Reyes-Gutierrez P, Johnston A, Martone C, Greto E, Quílez-Alvarez A, Calvo E, Bonzon-Kulichenko E, Álvarez-Velez R, Chooi M, Kwok I, González-Bermúdez B, Malleret B, Espinosa F, Zhang M, Wang Y, Sun D, Zhen Chong S, El-Armouche A, Kim K, Udalova I, Greco V, Garcia R, Vázquez J, Dopazo A, Plaza G, Alegre-Cebollada J, Uderhardt S, Ng L, Hidalgo A. Matrix-producing neutrophils populate and shield the skin. Nature 2025, 1-9. PMID: 40108463, DOI: 10.1038/s41586-025-08741-5.Peer-Reviewed Original ResearchRepertoire of proteinsExtracellular matrixInnate immune systemPopulation of neutrophilsImmune diversityPromote barrier functionBacterial invasionInnate immune cellsTGFB signalingForeign moleculesPhysical barrierRing formationBarrier functionImmune systemEnvironmental threatsDefenceDiverse strategiesToxic chemicalsNaive skinTGFBImmune cellsBacteriaNeutrophilsEnzymeProteinMolecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer
Iyer S, Wu J, Pollard T, Voth G. Molecular mechanism of Arp2/3 complex activation by nucleation-promoting factors and an actin monomer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2421467122. PMID: 40048273, PMCID: PMC11912402, DOI: 10.1073/pnas.2421467122.Peer-Reviewed Original ResearchConceptsArp2/3 complexActin monomersNeuronal Wiskott-Aldrich syndrome proteinWiskott-Aldrich syndrome proteinActin filament branchingMammalian Arp2/3 complexArp2/3 complex activationNucleation-promoting factorsActin-related proteinsCA motifsD-loopActin filamentsFilament branchingOrganelle movementBranch formationActive conformationActinMolecular mechanismsArp2/3Binding sitesArp3ProteinPathwayAtomistic molecular dynamics simulationsComplex activityFast Actin Disassembly and Fimbrin Mechanosensitivity Support Rapid Turnover in a Model of Clathrin‐Mediated Endocytosis
Mousavi S, Lacy M, Li X, Berro J. Fast Actin Disassembly and Fimbrin Mechanosensitivity Support Rapid Turnover in a Model of Clathrin‐Mediated Endocytosis. Cytoskeleton 2025 PMID: 40035221, DOI: 10.1002/cm.22002.Peer-Reviewed Original ResearchClathrin-mediated endocytosisActin filament disassemblyDynamics of actinActin-interacting proteinHigh membrane tensionActin meshworkEndocytic proteinsFilament disassemblyActin disassemblyNascent filamentsActin cytoskeletonEndocytic structuresEukaryotic cellsBinding partnersCellular processesTurgor pressureFimbrinActinRapid turnoverMembrane tensionEndocytosisProteinFilamentsDisassemblyYeastGuidelines for minimal reporting requirements, design and interpretation of experiments involving the use of eukaryotic dual gene expression reporters (MINDR)
Loughran G, Andreev D, Terenin I, Namy O, Mikl M, Yordanova M, McManus C, Firth A, Atkins J, Fraser C, Ignatova Z, Iwasaki S, Kufel J, Larsson O, Leidel S, Mankin A, Mariotti M, Tanenbaum M, Topisirovic I, Vázquez-Laslop N, Viero G, Caliskan N, Chen Y, Clark P, Dinman J, Farabaugh P, Gilbert W, Ivanov P, Kieft J, Mühlemann O, Sachs M, Shatsky I, Sonenberg N, Steckelberg A, Willis A, Woodside M, Valasek L, Dmitriev S, Baranov P. Guidelines for minimal reporting requirements, design and interpretation of experiments involving the use of eukaryotic dual gene expression reporters (MINDR). Nature Structural & Molecular Biology 2025, 32: 418-430. PMID: 40033152, DOI: 10.1038/s41594-025-01492-x.Peer-Reviewed Original ResearchConceptsInternal ribosome entry siteGene expression reportersStop codon readthroughRibosome entry siteEukaryotic translationTranscription initiationAntisense transcriptsRegulatory elementsRibosomal frameshiftingCodon readthroughExpression reportersEntry siteDual reportersUnconventional mechanismSequencePolyadenylationMisinterpretation of dataExpressionReadthroughFrameshiftSplicingTranscriptionEvaluate published dataMinimal requirementsProteinDrugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention
Bogin B, Levine Z. Drugging Disordered Proteins by Conformational Selection to Inform Therapeutic Intervention. Journal Of Chemical Theory And Computation 2025, 21: 3204-3215. PMID: 40029731, DOI: 10.1021/acs.jctc.4c01160.Peer-Reviewed Original ResearchConceptsIslet amyloid polypeptideIntrinsically disordered proteinsConformational selectionDisordered proteinsHuman islet amyloid polypeptideMolecular dynamics simulationsStable binding sitesSelf-assembling sequencesIAPP sequenceFixed conformationAmyloid polypeptideUmbrella samplingBinding preferencesConformational specificityTwo-state modelDynamics simulationsConformational heterogeneityNew conformationsBinding sitesMolecular binding mechanismsConformationBinding mechanismFoldamersStructural conformationProteinIdentification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities
Loesch D, Garg M, Matelska D, Vitsios D, Jiang X, Ritchie S, Sun B, Runz H, Whelan C, Holman R, Mentz R, Moura F, Wiviott S, Sabatine M, Udler M, Gause-Nilsson I, Petrovski S, Oscarsson J, Nag A, Paul D, Inouye M. Identification of plasma proteomic markers underlying polygenic risk of type 2 diabetes and related comorbidities. Nature Communications 2025, 16: 2124. PMID: 40032831, PMCID: PMC11876343, DOI: 10.1038/s41467-025-56695-z.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersCardiovascular DiseasesComorbidityDiabetes Mellitus, Type 2Extracellular Matrix ProteinsFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansInsulin-Like Growth Factor Binding Protein 2MaleMiddle AgedMultifactorial InheritanceProteomicsRisk FactorsUnited KingdomConceptsPolygenic scoresNon-coding variantsEtiology of type 2 diabetesMolecular dataVariant effectsPathway enrichmentPlasma proteomic markersPotential therapeutic targetType 2 diabetesProteinDisease biologyPolygenic riskUK BiobankProteomic markersTherapeutic targetPathwayCirculating proteinsGenomeRisk of type 2 diabetesCardiometabolic scoreBiologyInteractive portalVariantsEnrichmentDiabetes comorbiditiesInhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases
Johnson E, Nowar R, Viola K, Huang W, Zhou S, Bicca M, Zhu W, Kranz D, Klein W, Silverman R. Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2402117122. PMID: 40030015, PMCID: PMC11912461, DOI: 10.1073/pnas.2402117122.Peer-Reviewed Original ResearchConceptsProtein aggregationNeurodegenerative diseasesMechanisms of protein aggregationAmyloid-beta oligomersAlzheimer's disease neurodegenerationEndolysosomal traffickingBeta oligomersOligomer accumulationTreatment of neurodegenerative diseasesTDP-43Disease neurodegenerationPeptide aggregationLysosome-dependentCathepsin LProteinHippocampal neuronsPathological accumulationQuantitative assayTraffickingCellular mechanismsCathepsin BBlock neurodegenerationImmunofluorescence imagingPathogenic mechanismsNeurodegenerationProtein Folding as a Jamming Transition
Grigas A, Liu Z, Logan J, Shattuck M, O'Hern C. Protein Folding as a Jamming Transition. PRX Life 2025, 3: 013018. PMID: 38800654, PMCID: PMC11118678, DOI: 10.1103/prxlife.3.013018.Peer-Reviewed Original ResearchNorovirus co-opts NINJ1 for selective protein secretion
Song J, Zhang L, Moon S, Fang A, Wang G, Gheshm N, Loeb S, Cao P, Wallace J, Alfajaro M, Strine M, Beatty W, Jamieson A, Orchard R, Robinson B, Nice T, Wilen C, Orvedahl A, Reese T, Lee S. Norovirus co-opts NINJ1 for selective protein secretion. Science Advances 2025, 11: eadu7985. PMID: 40020060, PMCID: PMC11870086, DOI: 10.1126/sciadv.adu7985.Peer-Reviewed Original ResearchConceptsPlasma membrane ruptureDamage-associated molecular patternsNS1 secretionNinjurin-1Programmed cell deathAmino acid residuesViral replication sitesViral protein NS1CRISPR screensIntracellular viral proteinsMutagenesis studiesMembrane ruptureProtein NS1Unconventional pathwayCaspase-3Protein secretionViral proteinsReplication sitesCell deathMolecular patternsGenetic ablationNS1Pharmaceutical inhibitionDAMP releaseProteinTANGO2 is an acyl-CoA binding protein
Lujan A, Foresti O, Wojnacki J, Bigliani G, Brouwers N, Pena M, Androulaki S, Hashidate-Yoshida T, Kalyukina M, Novoselov S, Shindou H, Malhotra V. TANGO2 is an acyl-CoA binding protein. Journal Of Cell Biology 2025, 224: e202410001. PMID: 40015245, PMCID: PMC11867700, DOI: 10.1083/jcb.202410001.Peer-Reviewed Original ResearchConceptsAcyl-CoA binding proteinPeriphery of lipid dropletsAcyl-coenzyme A binding proteinA-binding proteinsAcyl-coenzyme AMitochondrial lumenHeme transportBinding proteinTANGO2Cellular localizationLipid dropletsStructural regionsLipid metabolismHeightened energy demandsMutationsProteinResiduesNrdEMetabolic crisisBindingMetabolismHemeSevere cardiomyopathyLipidThe pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network
Curwin A, Kurokawa K, Bigliani G, Brouwers N, Nakano A, Malhotra V. The pathway of unconventional protein secretion involves CUPS and a modified trans-Golgi network. Journal Of Cell Biology 2025, 224: e202312120. PMID: 40015244, PMCID: PMC11867701, DOI: 10.1083/jcb.202312120.Peer-Reviewed Original ResearchConceptsTrans-Golgi networkUnconventional protein secretionUnconventional secretionSuper-resolution confocal live imaging microscopyProtein secretionPhosphatidylinositol 3-phosphatePhosphatidylinositol 4-phosphateExtracts of membranesGolgi membranesConventional secretionGolgi cisternaeMembrane fusionSecreted proteinsCup formationPI4PRCY1Drs2GolgiProteinPhosphatidylinositolSecretionMembraneCOPIIImaging microscopyBiogenesisPolyamine metabolism is dysregulated in COXFA4-related mitochondrial disease
Marquez J, Viviano S, Beckman E, Thies J, Friedland-Little J, Lam C, Deniz E, Shelkowitz E. Polyamine metabolism is dysregulated in COXFA4-related mitochondrial disease. Human Genetics And Genomics Advances 2025, 6: 100418. PMID: 39967265, PMCID: PMC11946867, DOI: 10.1016/j.xhgg.2025.100418.Peer-Reviewed Original ResearchOrnithine decarboxylase pathwayCytochrome c oxidaseMitochondrial diseaseCause of mitochondrial diseaseAnalysis of cellular gene expressionSubunits of cytochrome c oxidaseC oxidaseTissue-specific diseasesCellular gene expressionDeficiency of cytochrome c oxidaseLeigh-like diseaseElectron donor NADHDownstream deficienciesMitochondrial membraneProtein complexesCellular functionsOxidative phosphorylationProtein subunitsGene expressionMetabolic pathwaysPolyamine metabolismPathwayProteinPoor growthAdenosine triphosphateDSP-1, the major fibronectin type-II protein of donkey seminal plasma is a small heat-shock protein and exhibits chaperone-like activity against thermal and oxidative stress
Alim S, Cheppali S, Pawar S, Swamy M. DSP-1, the major fibronectin type-II protein of donkey seminal plasma is a small heat-shock protein and exhibits chaperone-like activity against thermal and oxidative stress. Biochimica Et Biophysica Acta (BBA) - Proteins And Proteomics 2025, 1873: 141064. PMID: 39956303, DOI: 10.1016/j.bbapap.2025.141064.Peer-Reviewed Original ResearchConceptsChaperone-like activitySeminal plasmaFibronectin type IITetramer to monomersSperm capacitationSurface hydrophobicityMolecular chaperonesClient proteinsHeat shock proteinsBiophysical studiesAlcohol dehydrogenaseOxidative stressPhysiological ligandsShock proteinsProteinHead group moietySHspsBinding of phosphorylcholineCholine phospholipidsBindingFibronectinDehydrogenaseChaperoneSpermMammalsPhysiologic mechanisms underlying polycystic kidney disease
Boletta A, Caplan M. Physiologic mechanisms underlying polycystic kidney disease. Physiological Reviews 2025 PMID: 39938884, DOI: 10.1152/physrev.00018.2024.Peer-Reviewed Original ResearchPrimary ciliaPolycystic kidney diseaseTrafficking of proteinsHuman ciliopathiesExtracellular signalsMultiple genesKidney diseaseProtein productionMolecular basisCell biologyMonogenic disordersCyst formationGenesRenal epithelial cellsProteinCiliaBiochemical informationApical surfaceEpithelial cellsFunctional expressionPhysiological propertiesWealth of informationPhysiological mechanismsCellsFibrocystinMultimodal MRI accurately identifies amyloid status in unbalanced cohorts in Alzheimer’s disease continuum
Dolci G, Ellis C, Cruciani F, Brusini L, Abrol A, Galazzo I, Menegaz G, Calhoun V, . Multimodal MRI accurately identifies amyloid status in unbalanced cohorts in Alzheimer’s disease continuum. Network Neuroscience 2025, 9: 259-279. PMCID: PMC11949592, DOI: 10.1162/netn_a_00423.Peer-Reviewed Original ResearchNeuropathological hallmarks of Alzheimer's diseaseHallmarks of Alzheimer's diseaseHyperphosphorylated tau proteinAmyloid-bTau proteinNeurofibrillary tanglesNeuropathological hallmarksAmyloid accumulationAlzheimer's diseaseAb accumulationDepositional signatureIdentification of individualsAmyloid statusAccumulationAmyloidShed lightTanglesAlzheimer's disease continuumProteinMolecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse
Hanke-Gogokhia C, Zapadka T, Finkelstein S, Arshavsky V, Demb J. Molecular Components of Vesicle Cycling at the Rod Photoreceptor Ribbon Synapse. Advances In Experimental Medicine And Biology 2025, 1468: 325-330. PMID: 39930217, DOI: 10.1007/978-3-031-76550-6_54.Peer-Reviewed Original ResearchConceptsSynaptic vesicle exocytosisSynaptic vesicle recyclingPhotoreceptor ribbon synapseVesicle exocytosisVesicle recyclingVesicle cycleVesicle releaseRibbon synapseProtein synthesisProperties of synaptic transmissionMolecular componentsMouse rodsSynaptic terminalsRod cellsProteinVesiclesRod photoreceptorsDim lightSynaptic transmissionInner segmentsCellsExocytosisEndocytosisOuter segmentsEnergy productionHuman and mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome
Yarbro J, Han X, Dasgupta A, Yang K, Liu D, Shrestha H, Zaman M, Wang Z, Yu K, Lee D, Vanderwall D, Niu M, Sun H, Xie B, Chen P, Jiao Y, Zhang X, Wu Z, Chepyala S, Fu Y, Li Y, Yuan Z, Wang X, Poudel S, Vagnerova B, He Q, Tang A, Ronaldson P, Chang R, Yu G, Liu Y, Peng J. Human and mouse proteomics reveals the shared pathways in Alzheimer’s disease and delayed protein turnover in the amyloidome. Nature Communications 2025, 16: 1533. PMID: 39934151, PMCID: PMC11814087, DOI: 10.1038/s41467-025-56853-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProtein turnoverMouse model of amyloidosisMulti-omics analysisMurine model of Alzheimer's diseaseModel of Alzheimer's diseaseModel of amyloidosisProteome turnoverMouse proteomeGenetic incorporationAD pathwayAmyloid formationBrain proteomeMulti-omicsProteomic strategyAD progressionProteomicsProtein alterationsProteinDisease mechanismsAmyloidPathwayPotential targetMouse brainTurnoverProtein codes promote selective subcellular compartmentalization
Kilgore H, Chinn I, Mikhael P, Mitnikov I, Van Dongen C, Zylberberg G, Afeyan L, Banani S, Wilson-Hawken S, Lee T, Barzilay R, Young R. Protein codes promote selective subcellular compartmentalization. Science 2025, 387: 1095-1101. PMID: 39913643, DOI: 10.1126/science.adq2634.Peer-Reviewed Original ResearchConceptsProtein sequencesSubcellular compartmentsDiverse subcellular compartmentsProtein language modelsAmino acid sequenceProtein codingAcid sequenceSubcellular localizationDiverse proteinsHuman proteinsSubcellular compartmentalizationFolding codePathological mutationsCompartment localizationProteinSequenceCompartmentMutationsAminoNucleolusCompartmentalizationCellsTracing the origins of fibrotic fibroblasts: does the name matter? Look at the genes!
Mailleux A, Justet A. Tracing the origins of fibrotic fibroblasts: does the name matter? Look at the genes! European Respiratory Journal 2025, 65: 2402170. PMID: 39915043, DOI: 10.1183/13993003.02170-2024.Peer-Reviewed Original Research
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