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 localizationSecretionMembrane
2017
Cortical actin recovery at the immunological synapse leads to termination of lytic granule secretion in cytotoxic T lymphocytes
Ritter A, Kapnick S, Murugesan S, Schwartzberg P, Griffiths G, Lippincott-Schwartz J. Cortical actin recovery at the immunological synapse leads to termination of lytic granule secretion in cytotoxic T lymphocytes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2017, 114: e6585-e6594. PMID: 28716933, PMCID: PMC5559056, DOI: 10.1073/pnas.1710751114.Peer-Reviewed Original ResearchConceptsActin recoveryCD8<sup>+</sup> cytotoxic T lymphocytesGranule secretionImmunological synapseDepolymerization of actinLytic granule secretionCortical actin densityPhosphatidylinositol 4,5-bisphosphateCytotoxic T lymphocytesTotal internal reflection fluorescenceCortical actinActin clearanceGranule fusionActin densityKill multiple targetsImmune synapseActinT lymphocytesLytic granulesSuperresolution microscopyInfected cellsReflection fluorescenceVirally infected cellsSynapseCytotoxic granulesDynamic modulation of cortical actin at the immunological synapse controls lytic granule secretion in cytotoxic T lymphocytes
Kapnick S, Ritter A, Griffiths G, Lippincott-Schwartz J, Schwartzberg P. Dynamic modulation of cortical actin at the immunological synapse controls lytic granule secretion in cytotoxic T lymphocytes. The Journal Of Immunology 2017, 198: 151.4-151.4. DOI: 10.4049/jimmunol.198.supp.151.4.Peer-Reviewed Original ResearchCortical actinLytic granule secretionGranule fusionGranule secretionRecovery of actinActin regulatory proteinsClearance of actinActin recoveryActin cytoskeletonCD8+ cytotoxic T lymphocytesPolarized secretionRegulatory proteinsKill multiple targetsTIRF microscopyFluorescent reportersLytic proteinsActinImmunological synapseRAB27A mutationsSpecialized granulesSecretion granulesInfected cellsKill cellsVirally infected cellsCytotoxic T lymphocytes
2015
Munc18‐2 is required for Syntaxin 11 Localization on the Plasma Membrane in Cytotoxic T‐Lymphocytes
Dieckmann N, Hackmann Y, Aricò M, Griffiths G. Munc18‐2 is required for Syntaxin 11 Localization on the Plasma Membrane in Cytotoxic T‐Lymphocytes. Traffic 2015, 16: 1330-1341. PMID: 26771955, PMCID: PMC4791091, DOI: 10.1111/tra.12337.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesPlasma membraneMunc18-2Granule secretionT lymphocytesMunc18Syntaxin-11Fusion eventsFamilial haemophagocytic lymphohistiocytosisEndogenous localizationSyntaxinImmunological synapseSTX11Cytolytic granulesFHL4Loss of proteinHaemophagocytic lymphohistiocytosisPrimary immunodeficiencyProteinFHL5MembraneSecretionPlasmaLocalizationCytotoxicityActin 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
2005
Normal Lytic Granule Secretion by Cytotoxic T Lymphocytes Deficient in BLOC‐1, ‐2 and ‐3 and Myosins Va, VIIa and XV
Bossi G, Booth S, Clark R, Davis E, Liesner R, Richards K, Starcevic M, Stinchcombe J, Trambas C, Dell'Angelica E, Griffiths G. Normal Lytic Granule Secretion by Cytotoxic T Lymphocytes Deficient in BLOC‐1, ‐2 and ‐3 and Myosins Va, VIIa and XV. Traffic 2005, 6: 243-251. PMID: 15702992, DOI: 10.1111/j.1600-0854.2005.00264.x.Peer-Reviewed Original ResearchConceptsCytotoxic T lymphocytesBLOC-1Mouse model of Hermansky-Pudlak syndromeModel of Hermansky-Pudlak syndromeT lymphocytesLysosome-related organellesLytic granule secretionCytotoxic T lymphocyte functionPale ear miceUnconventional myosinBLOC-3Protein machineryBLOC-2Myosin VaSecretory lysosomesSecretory organellesAP-3Ruby-eyeHermansky-Pudlak syndromeDisplay defectsHPS patientsGranule secretionPlatelet functionSandy miceMouse model
2001
The Immunological Synapse of CTL Contains a Secretory Domain and Membrane Bridges
Stinchcombe J, Bossi G, Booth S, Griffiths G. The Immunological Synapse of CTL Contains a Secretory Domain and Membrane Bridges. Immunity 2001, 15: 751-761. PMID: 11728337, DOI: 10.1016/s1074-7613(01)00234-5.Peer-Reviewed Original ResearchConceptsImmunological synapseLytic granule secretionPlasma membrane markersTarget cell deathSecretory domainTarget cell membraneProtein organizationCytotoxic T lymphocytesAdhesive ringAdhesion proteinsCell deathMembrane bridgesGranule secretionMembrane markersCell contactMolecule domainsCell membraneFixed cell studiesCellsExocytosisCell studiesMembraneDomainProteinTarget
1993
Aspirin Does Not Inhibit Adenosine Diphosphate-Induced Platelet α-Granule Release
Rinder C, Student L, Bonan J, Rinder H, Smith B. Aspirin Does Not Inhibit Adenosine Diphosphate-Induced Platelet α-Granule Release. Blood 1993, 82: 505-512. PMID: 7687162, DOI: 10.1182/blood.v82.2.505.505.Peer-Reviewed Original ResearchConceptsP-selectin expressionAlpha-granule secretionPlatelet alpha-granule secretionAspirin treatmentP-selectinGranule secretionPlatelet alpha-granule releaseArachidonic acidCyclooxygenase-dependent metabolitesPlatelet surface expressionPlatelet α-granule releasePlatelet dense granule secretionAlpha-granule releaseΑ-granule releaseDense granule secretionPolymorphonuclear lymphocytesAmiloride treatmentLipoxygenase inhibitorsAspirinSecretionWhole bloodPlatelet-platelet interactionsTreatmentInvolvement of metabolitesPlateletsAspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release
Rinder C, Student L, Bonan J, Rinder H, Smith B. Aspirin does not inhibit adenosine diphosphate-induced platelet alpha- granule release. Blood 1993, 82: 505-512. DOI: 10.1182/blood.v82.2.505.bloodjournal822505.Peer-Reviewed Original ResearchP-selectin expressionAlpha-granule secretionPlatelet alpha-granule secretionAspirin treatmentP-selectinGranule secretionPlatelet alpha-granule releaseArachidonic acidCyclooxygenase-dependent metabolitesPlatelet surface expressionPlatelet dense granule secretionAlpha-granule releaseDense granule secretionPolymorphonuclear lymphocytesAmiloride treatmentLipoxygenase inhibitorsAspirinSecretionWhole bloodPlatelet-platelet interactionsTreatmentInvolvement of metabolitesPlateletsExpressionADP
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