2025
Dissecting the stress granule RNA world: dynamics, strategies and data
Biancon G, Busarello E, Cheng M, Halene S, Tebaldi T. Dissecting the stress granule RNA world: dynamics, strategies and data. RNA 2025, 31: rna.080409.125. PMID: 40086831, PMCID: PMC12084887, DOI: 10.1261/rna.080409.125.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCytoplasmic GranulesHumansRibonucleoproteinsRNARNA-Binding ProteinsRNA, MessengerStress GranulesStress, PhysiologicalTranscriptomeConceptsStress granulesRNA worldRegulation of gene expressionRNA-binding proteinsCytoplasmic ribonucleoprotein granulesRibonucleoprotein granulesTranscriptome dataRNA componentSG dynamicsCell signalingSG compositionSG componentsGene expressionCellular adaptationHuman diseasesStress conditionsExperimental strategiesRNAProteinComprehensive understandingMRNAGranulesRegulation
2022
Liquid–liquid phase separation facilitates the biogenesis of secretory storage granules
Parchure A, Tian M, Stalder D, Boyer C, Bearrows S, Rohli K, Zhang J, Rivera-Molina F, Ramazanov B, Mahata S, Wang Y, Stephens S, Gershlick D, von Blume J. Liquid–liquid phase separation facilitates the biogenesis of secretory storage granules. Journal Of Cell Biology 2022, 221: e202206132. PMID: 36173346, PMCID: PMC9526250, DOI: 10.1083/jcb.202206132.Peer-Reviewed Original ResearchMeSH KeywordsChromograninsCytoplasmic GranulesGolgi ApparatusHumansInsulinInsulin-Secreting CellsProinsulinSecretory VesiclesConceptsTrans-Golgi networkLiquid-liquid phase separationSecretory granulesClient moleculesSecretory storage granulesΒ-cellsMembrane traffickingCargo receptorsPlasma membranePancreatic β-cellsProcessing enzymesCell typesStorage granulesChromogranin proteinsBiogenesisAcidic pHTraffickingGranulesProteinEnzyme
2020
Factor V activity in apheresis platelets: Implications for management of FV deficiency
Gupta GK, Hendrickson JE, Bahel P, Siddon AJ, Rinder HM, Tormey CA. Factor V activity in apheresis platelets: Implications for management of FV deficiency. Transfusion 2020, 61: 405-409. PMID: 33166428, DOI: 10.1111/trf.16179.Peer-Reviewed Original ResearchProgrammed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation
Adrover JM, Aroca-Crevillén A, Crainiciuc G, Ostos F, Rojas-Vega Y, Rubio-Ponce A, Cilloniz C, Bonzón-Kulichenko E, Calvo E, Rico D, Moro MA, Weber C, Lizasoaín I, Torres A, Ruiz-Cabello J, Vázquez J, Hidalgo A. Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation. Nature Immunology 2020, 21: 135-144. PMID: 31932813, PMCID: PMC7223223, DOI: 10.1038/s41590-019-0571-2.Peer-Reviewed Original ResearchConceptsMagnitude of inflammationNeutrophil extracellular trapsNeutrophil proteomeGranule contentsInflammatory injuryRespiratory distressPneumonia patientsExtracellular trapsCell-intrinsic programsProgressive lossHuman neutrophilsNET formationProtein storesNeutrophilsInflammationLungAntimicrobial functionMouse mutantsCircadian cyclePatientsInjuryTime of dayArmamentariumIncidenceSeverity
2019
Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis
Fritzlar S, Aktepe TE, Chao YW, Kenney ND, McAllaster MR, Wilen CB, White PA, Mackenzie JM. Mouse Norovirus Infection Arrests Host Cell Translation Uncoupled from the Stress Granule-PKR-eIF2α Axis. MBio 2019, 10: 10.1128/mbio.00960-19. PMID: 31213553, PMCID: PMC6581855, DOI: 10.1128/mbio.00960-19.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCaliciviridae InfectionsCytoplasmic GranulesDNA HelicaseseIF-2 KinaseEukaryotic Initiation Factor-2Host-Pathogen InteractionsImmune EvasionImmunity, InnateMicePhosphorylationPoly-ADP-Ribose Binding ProteinsProtein BiosynthesisRNA HelicasesRNA Recognition Motif ProteinsViral ProteinsVirus ReplicationConceptsIntegrated stress responseProtein kinase RStress granulesProtein translationCellular homeostasisProtein G3BP1Host translationCytoplasmic RNA granulesMNV replication complexHijack host machineryPhosphorylation of eIF2αHost protein translationCellular response systemsHost cell translationEukaryotic initiation factorMNV infectionPhosphorylated eukaryotic initiation factorRNA granulesTranslational controlSG formationInitiation factorsSG nucleationTranslational arrestHost machineryVirus replicationPhospholipids: Pulling Back the Actin Curtain for Granule Delivery to the Immune Synapse
Gawden-Bone C, Griffiths G. Phospholipids: Pulling Back the Actin Curtain for Granule Delivery to the Immune Synapse. Frontiers In Immunology 2019, 10: 700. PMID: 31031745, PMCID: PMC6470250, DOI: 10.3389/fimmu.2019.00700.Peer-Reviewed Original ResearchConceptsImmune synapsePlasma membraneSignaling eventsPhospholipid phosphatidylserineInner leafletPhosphatidic acidCellular responsesGranule deliveryCell functionImmune cell functionExtracellular changesFunction of cytotoxic T lymphocytesMembrane changesCytotoxic T lymphocytesMembraneSynapseCytoskeletonT lymphocytesActinPhosphoinositideDiacylglycerolPhosphatidylserineMessengerUncoupling of nucleo-cytoplasmic RNA export and localization during stress
Hochberg-Laufer H, Schwed-Gross A, Neugebauer KM, Shav-Tal Y. Uncoupling of nucleo-cytoplasmic RNA export and localization during stress. Nucleic Acids Research 2019, 47: 4778-4797. PMID: 30864659, PMCID: PMC6511838, DOI: 10.1093/nar/gkz168.Peer-Reviewed Original ResearchConceptsRNA-binding proteinStress granulesNuclear specklesMRNA exportFormation of SGsCytoplasmic stress granulesSub-cellular compartmentsGene expression pathwaysMRNA export adaptorsComplex recruitmentEukaryotic cellsRNA exportRNA metabolismExport adaptorGranule assemblyNuclear proteinsExpression pathwaysRNAStress inductionMRNACytoplasmProteinPotent inhibitorCellsNucleoporins
2018
PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes
Gawden-Bone C, Frazer G, Richard A, Y. C, Strege K, Griffiths G. PIP5 Kinases Regulate Membrane Phosphoinositide and Actin Composition for Targeted Granule Secretion by Cytotoxic Lymphocytes. Immunity 2018, 49: 427-437.e4. PMID: 30217409, PMCID: PMC6162341, DOI: 10.1016/j.immuni.2018.08.017.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell DegranulationCell LineCell MembraneCytoplasmic GranulesCytotoxicity, ImmunologicImmunological SynapsesLymphocyte ActivationMiceMice, Inbred C57BLMice, TransgenicPhosphatidylinositolsPhosphotransferases (Alcohol Group Acceptor)Receptors, Antigen, T-CellSignal TransductionT-Lymphocytes, CytotoxicConceptsPlasma membraneGranule secretionSynapse formationT cell receptorArea of plasma membraneT cell receptor signalingImmune synapse formationActin depletionActin recruitmentPhosphoinositide compositionPIP5-kinaseCytotoxic T lymphocytesMembrane phosphoinositidesPI(4,5)P2Centrosome dockingActinTCR activationCell receptorsIncreased diacylglycerolPhosphoinositideSynapseDiacylglycerolForce localizationSecretionMembraneFas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse
Lee J, Dieckmann N, Edgar J, Griffiths G, Siegel R. Fas Ligand localizes to intraluminal vesicles within NK cell cytolytic granules and is enriched at the immune synapse. Immunity Inflammation And Disease 2018, 6: 312-321. PMID: 29642281, PMCID: PMC5946154, DOI: 10.1002/iid3.219.Peer-Reviewed Original ResearchConceptsIntraluminal vesiclesImmune synapseCytolytic granulesImmune synapsesCognate receptor FasType II transmembrane proteinFormation of immune synapsesMembrane-bound FasLNK cellsPerforin-containing granulesIntra-luminal vesiclesReceptor FasFusion proteinTransmembrane proteinsB cellsPlasma membraneFas ligandFasLImmunoelectron microscopyNK cell cytotoxicityHuman NK cellsFASDense-coreVesiclesPerforin/granzyme systemP‑Bodies: Composition, Properties, and Functions
Luo Y, Na Z, Slavoff SA. P‑Bodies: Composition, Properties, and Functions. Biochemistry 2018, 57: 2424-2431. PMID: 29381060, PMCID: PMC6296482, DOI: 10.1021/acs.biochem.7b01162.Peer-Reviewed Original ResearchMeSH KeywordsCytoplasmic GranulesGene Expression RegulationProteinsRibonucleoproteinsRNA Processing, Post-TranscriptionalRNA StabilityRNA, MessengerConceptsP-bodiesMRNA decayMRNA decay machineryLiquid-liquid phase separationP-body functionPost-transcriptional regulationDecay machineryProcessing bodiesTranslational repressionEukaryotic cellsCytoplasmic ribonucleoproteinCellular localizationRibonucleoproteinMolecular compositionRecent advancesRepressionMachineryProteinMRNARegulationFunctionCellsLocalizationDiscoveryComposition
2017
Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex
Ryan KE, Kim PS, Fleming JT, Brignola E, Cheng FY, Litingtung Y, Chiang C. Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex. Developmental Biology 2017, 432: 165-177. PMID: 28974424, PMCID: PMC5694378, DOI: 10.1016/j.ydbio.2017.09.036.Peer-Reviewed Original ResearchThe Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis
Stephens SB, Edwards RJ, Sadahiro M, Lin WJ, Jiang C, Salton SR, Newgard CB. The Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis. Cell Reports 2017, 20: 2480-2489. PMID: 28877479, PMCID: PMC5624795, DOI: 10.1016/j.celrep.2017.08.050.Peer-Reviewed Original ResearchAmyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons
Gopal PP, Nirschl JJ, Klinman E, Holzbaur EL. Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e2466-e2475. PMID: 28265061, PMCID: PMC5373408, DOI: 10.1073/pnas.1614462114.Peer-Reviewed Original ResearchConceptsRNA-binding proteinRNP granulesAmyotrophic lateral sclerosis-linked mutationsCritical cellular processesRapid fluorescence recoveryAmyotrophic lateral sclerosisBiophysical propertiesDistinct biophysical propertiesRibonucleoprotein granulesSubcellular contextCellular processesSpecific RNAToxic gainTAR-DNA binding protein 43Superresolution microscopyFluorescence recoveryLiquid-liquid phase separationMutant TDP-43Primary cortical neuronsLiquid-like propertiesTDP-43RNAProteinMutationsAxonal location
2015
Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis
Fan F, Ji C, Wu Y, Ferguson SM, Tamarina N, Philipson LH, Lou X. Dynamin 2 regulates biphasic insulin secretion and plasma glucose homeostasis. Journal Of Clinical Investigation 2015, 125: 4026-4041. PMID: 26413867, PMCID: PMC4639984, DOI: 10.1172/jci80652.Peer-Reviewed Original ResearchConceptsDynamin 2Glucose-stimulated insulin secretionΒ-cellsExocytosis-endocytosis couplingControl β-cellsMutant β-cellsCell surface expansionF-actin remodelingInsulin granule exocytosisEndocytic intermediatesMembrane fissionInsulin granule recruitmentPancreatic β-cell dysfunctionPlasma membraneActin filamentsBiphasic insulin secretionInsulin granulesGene ablationΒ-cell dysfunctionGranule recruitmentGlucose homeostasisBlood glucose homeostasisEndocytosisGranule exocytosisEssential roleActin Depletion Initiates Events Leading to Granule Secretion at the Immunological Synapse
Ritter A, Asano Y, Stinchcombe J, Dieckmann N, Chen B, Gawden-Bone C, van Engelenburg S, Legant W, Gao L, Davidson M, Betzig E, Lippincott-Schwartz J, Griffiths G. Actin Depletion Initiates Events Leading to Granule Secretion at the Immunological Synapse. Immunity 2015, 42: 864-876. PMID: 25992860, PMCID: PMC4448150, DOI: 10.1016/j.immuni.2015.04.013.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesT cell receptorActin-rich projectionsCortical actin densityActin depletionCortical actinCentrosome polarizationPolarized secretionActin densityIntracellular vesiclesRegulate secretionCentrosomeImmunological synapseActinSynapse maturationGranule secretionT lymphocytesTumor cellsPhospholipid PIP2Area of membraneSynapseSecretionCSMACHigh-resolution 4D imagingInitial event
2014
Polarized Granzyme Release Is Required for Antigen-Driven Transendothelial Migration of Human Effector Memory CD4 T Cells
Manes TD, Pober JS. Polarized Granzyme Release Is Required for Antigen-Driven Transendothelial Migration of Human Effector Memory CD4 T Cells. The Journal Of Immunology 2014, 193: 5809-5815. PMID: 25367116, PMCID: PMC4258477, DOI: 10.4049/jimmunol.1401665.Peer-Reviewed Original ResearchConceptsEffector memory CD4 T cellsMemory CD4 T cellsCD4 T cellsT cellsTransendothelial migrationImmune synapse formationEndothelial cell monolayersInflammatory chemokinesMorphologic manifestationsGranzyme releaseSynapse formationTCR recognitionGranule dischargeDynein-driven transportChemokinesCell monolayersEarly eventsEndotheliumCytosolic granulesCellsMTOC reorientationProteolytic activityMicrotubule organizing centerMolecular requirementsGranule function
2013
Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity
Tuli A, Thiery J, James A, Michelet X, Sharma M, Garg S, Sanborn K, Orange J, Lieberman J, Brenner M. Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell–mediated cytotoxicity. Molecular Biology Of The Cell 2013, 24: 3721-3735. PMID: 24088571, PMCID: PMC3842998, DOI: 10.1091/mbc.e13-05-0259.Peer-Reviewed Original ResearchConceptsLysosome-related organellesMicrotubule-organizing centerImmune synapseKinesin-1Lytic granulesPolarization of lytic granulesGTP-binding proteinsPull-down approachMovement of lysosomesGranule polarizationLytic granule polarizationKinesin family member 5BNatural killer cell-mediated cytotoxicityNK cell lysatesFormation of immune synapseADP-ribosylationTripartite complexArl8bTarget cell membraneInteraction partnersAnterograde movementCell lysatesTarget cellsMember 5BCell membraneIdentification of SERPINB1 As a Physiological Inhibitor of Human Granzyme H
Wang L, Li Q, Wu L, Liu S, Zhang Y, Yang X, Zhu P, Zhang H, Zhang K, Lou J, Liu P, Tong L, Sun F, Fan Z. Identification of SERPINB1 As a Physiological Inhibitor of Human Granzyme H. The Journal Of Immunology 2013, 190: 1319-1330. PMID: 23269243, DOI: 10.4049/jimmunol.1202542.Peer-Reviewed Original ResearchCatalysisCell Line, TumorChromatography, GelCrystallography, X-RayCytoplasmic GranulesCytotoxicity, ImmunologicGenetic VectorsGranzymesHumansJurkat CellsKiller Cells, Lymphokine-ActivatedModels, MolecularNeoplasm ProteinsProtein BindingProtein ConformationProtein Interaction MappingRecombinant Fusion ProteinsSerpinsStructure-Activity Relationship
2012
Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation
Lui‐Roberts W, Stinchcombe J, Ritter A, Akhmanova A, Karakesisoglou I, Griffiths G. Cytotoxic T lymphocyte effector function is independent of nucleus–centrosome dissociation. European Journal Of Immunology 2012, 42: 2132-2141. PMID: 22736282, PMCID: PMC3470926, DOI: 10.1002/eji.201242525.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesCentral supramolecular activation complexImmunological synapseCytotoxic T lymphocyte effector functionCytotoxic T lymphocyte cytotoxicityCytotoxic T lymphocyte killingT lymphocyte effector functionsSecretion of lytic granules contentSupramolecular activation complexVirally infected cellsLytic granule contentsT lymphocytesEffector functionsMock-treated cellsTarget cellsInfected cellsImmunofluorescence microscopyCell typesGranule contentsCellsSecretionRelease granulesSynapseNuclear membraneCentrosome docking
2011
Familial hemophagocytic lymphohistiocytosis: a model for understanding the human machinery of cellular cytotoxicity
Sieni E, Cetica V, Mastrodicasa E, Pende D, Moretta L, Griffiths G, Aricò M. Familial hemophagocytic lymphohistiocytosis: a model for understanding the human machinery of cellular cytotoxicity. Cellular And Molecular Life Sciences 2011, 69: 29-40. PMID: 21990010, PMCID: PMC11114696, DOI: 10.1007/s00018-011-0835-y.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChediak-Higashi SyndromeCytoplasmic GranulesCytotoxicity, ImmunologicHermanski-Pudlak SyndromeHumansImmunologic Deficiency SyndromesKiller Cells, NaturalLymphocyte SubsetsLymphohistiocytosis, HemophagocyticLymphoproliferative DisordersMacrophage Activation SyndromeMembrane ProteinsMiceMunc18 ProteinsNatural Killer T-CellsPerforinPiebaldismPore Forming Cytotoxic ProteinsPrimary Immunodeficiency DiseasesQa-SNARE ProteinsT-Lymphocytes, CytotoxicConceptsCellular cytotoxicityGenetic immune deficienciesCellular cytotoxic mechanismsCytotoxic T lymphocytesNatural killer cellsKill infected cellsFamilial hemophagocytic lymphohistiocytosisInherited human disordersNKT cellsHemophagocytic lymphohistiocytosisProspective trialsEffector cellsImmune deficiencyKiller cellsT lymphocytesClinical pictureRare diseaseClinical syndromeTherapeutic approachesImprove outcomesGenetic subsetsGenetic studiesCytotoxic mechanismInfected cellsHuman disorders
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