2021
ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes
Shi F, Mendrola JM, Sheetz JB, Wu N, Sommer A, Speer KF, Noordermeer JN, Kan ZY, Perry K, Englander SW, Stayrook SE, Fradkin LG, Lemmon MA. ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes. Cell Reports 2021, 37: 109834. PMID: 34686333, PMCID: PMC8650758, DOI: 10.1016/j.celrep.2021.109834.Peer-Reviewed Original ResearchAnimalsDrosophila melanogasterDrosophila ProteinsModels, MolecularNerve Tissue ProteinsProtein BindingProtein ConformationProtein Interaction Domains and MotifsProtein-Tyrosine KinasesProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesSf9 CellsStructure-Activity RelationshipWnt ProteinsWnt Signaling Pathway
2019
Mutagenesis of the ADAM17-phosphatidylserine–binding motif leads to embryonic lethality in mice
Veit M, Ahrens B, Seidel J, Sommer A, Bhakdi S, Reiss K. Mutagenesis of the ADAM17-phosphatidylserine–binding motif leads to embryonic lethality in mice. Life Science Alliance 2019, 2: e201900430. PMID: 31455669, PMCID: PMC6712283, DOI: 10.26508/lsa.201900430.Peer-Reviewed Original ResearchConceptsEmbryonic lethalityVital cellular functionsAnionic phospholipid headgroupsTransmembrane substratesCellular functionsProtease functionBinding motifAmino acidsCell surfaceMutant proteasePrimary hepatocytesMotifMutagenesisPhosphatidylserinePhospholipid headgroupsProminent memberCentral roleEssential triggerLethalitySurface exposureOncogenesisProteaseADAM17DisintegrinMiceADAM10 sheddase activation is controlled by cell membrane asymmetry
Bleibaum F, Sommer A, Veit M, Rabe B, Andrä J, Kunzelmann K, Nehls C, Correa W, Gutsmann T, Grötzinger J, Bhakdi S, Reiss K. ADAM10 sheddase activation is controlled by cell membrane asymmetry. Journal Of Molecular Cell Biology 2019, 11: 979-993. PMID: 30753537, PMCID: PMC6927242, DOI: 10.1093/jmcb/mjz008.Peer-Reviewed Original ResearchNon-acylated Wnts Can Promote Signaling
Speer KF, Sommer A, Tajer B, Mullins MC, Klein PS, Lemmon MA. Non-acylated Wnts Can Promote Signaling. Cell Reports 2019, 26: 875-883.e5. PMID: 30673610, PMCID: PMC6429962, DOI: 10.1016/j.celrep.2018.12.104.Peer-Reviewed Original Research
2018
Smoothening out the patches
Sommer A, Lemmon MA. Smoothening out the patches. Science 2018, 362: 26-27. PMID: 30287647, PMCID: PMC6421564, DOI: 10.1126/science.aav1025.Peer-Reviewed Original ResearchConceptsProtein PatchedTransmembrane protein PatchedCryo-electron microscopyRecent crystal structureUnique molecular mechanismImportant tumor suppressorKey HedgehogImportant new insightsMolecular mechanismsTumor suppressorMolecular eventsHedgehogCell membranePathwayCholesterol transportNew insightsNew roleHomologous ligandsMetazoansPatchedSmoothenedSuppressorRecent reportsProteinCrystal structureAnoctamin-6 regulates ADAM sheddase function
Veit M, Koyro K, Ahrens B, Bleibaum F, Munz M, Rövekamp H, Andrä J, Schreiber R, Kunzelmann K, Sommer A, Bhakdi S, Reiss K. Anoctamin-6 regulates ADAM sheddase function. Biochimica Et Biophysica Acta (BBA) - Molecular Cell Research 2018, 1865: 1598-1610. PMID: 30327201, DOI: 10.1016/j.bbamcr.2018.08.011.Peer-Reviewed Original ResearchConceptsAnoctamin 6Scramblase activityHuman umbilical vein endothelial cellsTNF receptor 1Vital cellular functionsPhospholipid scramblase activityPS exposureHEK293T cellsTGF-alphaTransformation of cellsSheddase functionTransmembrane substratesCellular functionsADAM17 substratesPlasma membraneUmbilical vein endothelial cellsInhibitor experimentsSheddase activitySubstrate cleavageImportant regulatorVein endothelial cellsActivator PMAProminent memberAmphiregulinEndothelial cells
2017
Extracellular sphingomyelinase activity impairs TNF-α-induced endothelial cell death via ADAM17 activation and TNF receptor 1 shedding
Sommer A, Düppe M, Baumecker L, Kordowski F, Büch J, Chico J, Fritsch J, Schütze S, Adam D, Sperrhacke M, Bhakdi S, Reiss K. Extracellular sphingomyelinase activity impairs TNF-α-induced endothelial cell death via ADAM17 activation and TNF receptor 1 shedding. Oncotarget 2017, 5: 72584-72596. PMID: 29069811, PMCID: PMC5641154, DOI: 10.18632/oncotarget.19983.Peer-Reviewed Original ResearchHuman umbilical vein endothelial cellsEndothelial cell deathCell deathTNF-α receptor 1COS7 cellsVital cellular functionsPhospholipid scramblasesSheddase functionCellular functionsEffect of SMaseADAM activityExtracellular sphingomyelinaseSignaling cascadesEndothelial cellsUmbilical vein endothelial cellsReceptor 1Phospholipid asymmetryPS externalizationSheddase activityCell survivalImportant regulatorVein endothelial cellsCell typesEndothelial cell functionEndothelial cell proliferation
2016
How membrane asymmetry regulates ADAM17 sheddase function
Sommer A, Bhakdi S, Reiss K. How membrane asymmetry regulates ADAM17 sheddase function. Cell Cycle 2016, 15: 2995-2996. PMID: 27463373, PMCID: PMC5134693, DOI: 10.1080/15384101.2016.1211449.Peer-Reviewed Original ResearchPhosphatidylserine exposure is required for ADAM17 sheddase function
Sommer A, Kordowski F, Büch J, Maretzky T, Evers A, Andrä J, Düsterhöft S, Michalek M, Lorenzen I, Somasundaram P, Tholey A, Sönnichsen F, Kunzelmann K, Heinbockel L, Nehls C, Gutsmann T, Grötzinger J, Bhakdi S, Reiss K. Phosphatidylserine exposure is required for ADAM17 sheddase function. Nature Communications 2016, 7: 11523. PMID: 27161080, PMCID: PMC4866515, DOI: 10.1038/ncomms11523.Peer-Reviewed Original ResearchConceptsMembrane-proximal domainVital cellular functionsSheddase functionTransmembrane substratesCellular functionsScott syndromeSheddase activityProximal domainPhosphatidylserine exposureSurface-exposed phosphatidylserinePS exposurePhosphatidylserineProminent memberProteaseCellsRaji cellsCleavageSurface exposureDomain
2015
Extracellular Juxtamembrane Segment of ADAM17 Interacts with Membranes and Is Essential for Its Shedding Activity
Düsterhöft S, Michalek M, Kordowski F, Oldefest M, Sommer A, Röseler J, Reiss K, Grötzinger J, Lorenzen I. Extracellular Juxtamembrane Segment of ADAM17 Interacts with Membranes and Is Essential for Its Shedding Activity. Biochemistry 2015, 54: 5791-5801. PMID: 26348730, DOI: 10.1021/acs.biochem.5b00497.Peer-Reviewed Original ResearchConceptsMembrane-proximal domainJuxtamembrane segmentSubstrate recognitionMembrane-anchored proteinsAmino acid residuesActivity of ADAM17Extracellular regionBiological processesMajor sheddasesAcid residuesCancer progressionLipid bilayersMetalloprotease 17Key mediatorInterleukin-6 receptorDisintegrinADAM17SheddasesDomainProteinInteractsResiduesDifferentiationActivityWide variety
2012
Melittin Modulates Keratinocyte Function through P2 Receptor-dependent ADAM Activation*
Sommer A, Fries A, Cornelsen I, Speck N, Koch-Nolte F, Gimpl G, Andrä J, Bhakdi S, Reiss K. Melittin Modulates Keratinocyte Function through P2 Receptor-dependent ADAM Activation*. Journal Of Biological Chemistry 2012, 287: 23678-23689. PMID: 22613720, PMCID: PMC3390642, DOI: 10.1074/jbc.m112.362756.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAM10 ProteinADAM17 ProteinAdenosine TriphosphateAmyloid Precursor Protein SecretasesAnimalsBlotting, WesternCadherinsCell LineCell SurvivalCells, CulturedDose-Response Relationship, DrugEmbryo, MammalianErbB ReceptorsExtracellular Signal-Regulated MAP KinasesFibroblastsHEK293 CellsHumansKeratinocytesMelittenMembrane ProteinsMiceMice, KnockoutModels, BiologicalPhosphorylationReceptors, Purinergic P2X7Reverse Transcriptase Polymerase Chain ReactionConceptsAnti-cancer agentsP2 receptorsADAM activationP2 receptor antagonistsRelease of TGFMultiple cellular functionsPurinergic P2 receptorsAdhesion molecule E-cadherinE-cadherinReceptor antagonistP2X7 receptorHuman HaCaT keratinocytesCellular functionsPresence of ATPasesDownstream eventsATP releaseEGFR phosphorylationHuman neutrophilsEGF receptorEndothelial cellsERK1/2 phosphorylationKeratinocyte proliferationReceptorsBee venomCell migration
2011
Assessment of Endothelial Permeability and Leukocyte Transmigration in Human Endothelial Cell Monolayers
Ludwig A, Sommer A, Uhlig S. Assessment of Endothelial Permeability and Leukocyte Transmigration in Human Endothelial Cell Monolayers. Methods In Molecular Biology 2011, 763: 319-332. PMID: 21874462, DOI: 10.1007/978-1-61779-191-8_22.Peer-Reviewed Original ResearchCapillary PermeabilityCell Membrane PermeabilityCell MovementCells, CulturedDextransDiffusion Chambers, CultureElectric ImpedanceEndothelial CellsEndothelium, VascularFluorescenceHumansInflammationIntercellular JunctionsInterleukin-8LungMicroscopy, ConfocalNeutrophilsPermeabilityPotentiometryThrombin