Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments

DC FieldValueLanguage
dc.contributor.authorRichter, David
dc.contributor.authorMoraga, Ignacio
dc.contributor.authorWinkelmann, Hauke
dc.contributor.authorBirkholz, Oliver
dc.contributor.authorWilmes, Stephan
dc.contributor.authorSchulte, Markos
dc.contributor.authorKraich, Michael
dc.contributor.authorKenneweg, Hella
dc.contributor.authorBeutel, Oliver
dc.contributor.authorSelenschik, Philipp
dc.contributor.authorPaterok, Dirk
dc.contributor.authorGavutis, Martynas
dc.contributor.authorSchmidt, Thomas
dc.contributor.authorGarcia, K. Christopher
dc.contributor.authorMueller, Thomas D.
dc.contributor.authorPiehler, Jacob
dc.date.accessioned2021-12-23T16:21:14Z-
dc.date.available2021-12-23T16:21:14Z-
dc.date.issued2017
dc.identifier.issn20411723
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/13780-
dc.description.abstractThe spatiotemporal organization of cytokine receptors in the plasma membrane is still debated with models ranging from ligand-independent receptor pre-dimerization to ligand-induced receptor dimerization occurring only after receptor uptake into endosomes. Here, we explore the molecular and cellular determinants governing the assembly of the type II interleukin-4 receptor, taking advantage of various agonists binding the receptor subunits with different affinities and rate constants. Quantitative kinetic studies using artificial membranes confirm that receptor dimerization is governed by the two-dimensional ligand-receptor interactions and identify a critical role of the transmembrane domain in receptor dimerization. Single molecule localization microscopy at physiological cell surface expression levels, however, reveals efficient ligand-induced receptor dimerization by all ligands, largely independent of receptor binding affinities, in line with the similar STAT6 activation potencies observed for all IL-4 variants. Detailed spatiotemporal analyses suggest that kinetic trapping of receptor dimers in actin-dependent microcompartments sustains robust receptor dimerization and signalling.
dc.description.sponsorshipDeutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB 944]; HHMIHoward Hughes Medical Institute; BMBF project IlReMu; [NIH-RO1AI51321]; We thank Dr C. Berens for providing the Tet-inducible expression system, Dr R. Kurre for support with fluorescence microscopy, C. Reynolds and G. Hikade for excellent experimental support, C. P. Richter for providing single molecule localization and tracking tools and the members of the Piehler, Garcia and Muller laboratories for helpful advice and discussion. This project was supported by the SFB 944 (P8 and Z) from the Deutsche Forschungsgemeinschaft (to J.P.), NIH-RO1AI51321 and HHMI (to K.C.G.) as well as by the BMBF project IlReMu (to T.D.M.).
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofNATURE COMMUNICATIONS
dc.subjectCELL-SURFACE
dc.subjectERYTHROPOIETIN RECEPTOR
dc.subjectGROWTH-HORMONE RECEPTOR
dc.subjectLIVING CELLS
dc.subjectMODEL MEMBRANES
dc.subjectMultidisciplinary Sciences
dc.subjectPOLYMER-SUPPORTED MEMBRANES
dc.subjectRESONANCE ENERGY-TRANSFER
dc.subjectScience & Technology - Other Topics
dc.subjectSINGLE-MOLECULE TECHNIQUES
dc.subjectT-CELLS
dc.subjectTRANSMEMBRANE PROTEINS
dc.titleLigand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments
dc.typejournal article
dc.identifier.doi10.1038/ncomms15976
dc.identifier.isiISI:000405465400001
dc.description.volume8
dc.contributor.orcid0000-0003-1343-5719
dc.contributor.orcid0000-0002-0045-1851
dc.contributor.orcid0000-0003-3688-6854
dc.contributor.orcid0000-0001-9909-0701
dc.contributor.orcid0000-0002-4112-710X
dc.contributor.orcid0000-0001-6551-3219
dc.contributor.orcid0000-0003-1862-7357
dc.contributor.researcheridAAB-7126-2019
dc.contributor.researcheridB-6296-2009
dc.publisher.placeMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
dcterms.isPartOf.abbreviationNat. Commun.
dcterms.oaStatusGreen Published, gold
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.orcid0000-0002-2143-2270-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidPiJa938-
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