Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments
DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Richter, David | |
dc.contributor.author | Moraga, Ignacio | |
dc.contributor.author | Winkelmann, Hauke | |
dc.contributor.author | Birkholz, Oliver | |
dc.contributor.author | Wilmes, Stephan | |
dc.contributor.author | Schulte, Markos | |
dc.contributor.author | Kraich, Michael | |
dc.contributor.author | Kenneweg, Hella | |
dc.contributor.author | Beutel, Oliver | |
dc.contributor.author | Selenschik, Philipp | |
dc.contributor.author | Paterok, Dirk | |
dc.contributor.author | Gavutis, Martynas | |
dc.contributor.author | Schmidt, Thomas | |
dc.contributor.author | Garcia, K. Christopher | |
dc.contributor.author | Mueller, Thomas D. | |
dc.contributor.author | Piehler, Jacob | |
dc.date.accessioned | 2021-12-23T16:21:14Z | - |
dc.date.available | 2021-12-23T16:21:14Z | - |
dc.date.issued | 2017 | |
dc.identifier.issn | 20411723 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/13780 | - |
dc.description.abstract | The 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.sponsorship | Deutsche 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.iso | en | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.relation.ispartof | NATURE COMMUNICATIONS | |
dc.subject | CELL-SURFACE | |
dc.subject | ERYTHROPOIETIN RECEPTOR | |
dc.subject | GROWTH-HORMONE RECEPTOR | |
dc.subject | LIVING CELLS | |
dc.subject | MODEL MEMBRANES | |
dc.subject | Multidisciplinary Sciences | |
dc.subject | POLYMER-SUPPORTED MEMBRANES | |
dc.subject | RESONANCE ENERGY-TRANSFER | |
dc.subject | Science & Technology - Other Topics | |
dc.subject | SINGLE-MOLECULE TECHNIQUES | |
dc.subject | T-CELLS | |
dc.subject | TRANSMEMBRANE PROTEINS | |
dc.title | Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments | |
dc.type | journal article | |
dc.identifier.doi | 10.1038/ncomms15976 | |
dc.identifier.isi | ISI:000405465400001 | |
dc.description.volume | 8 | |
dc.contributor.orcid | 0000-0003-1343-5719 | |
dc.contributor.orcid | 0000-0002-0045-1851 | |
dc.contributor.orcid | 0000-0003-3688-6854 | |
dc.contributor.orcid | 0000-0001-9909-0701 | |
dc.contributor.orcid | 0000-0002-4112-710X | |
dc.contributor.orcid | 0000-0001-6551-3219 | |
dc.contributor.orcid | 0000-0003-1862-7357 | |
dc.contributor.researcherid | AAB-7126-2019 | |
dc.contributor.researcherid | B-6296-2009 | |
dc.publisher.place | MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND | |
dcterms.isPartOf.abbreviation | Nat. Commun. | |
dcterms.oaStatus | Green Published, gold | |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.netid | PiJa938 | - |
Seitenaufrufe
3
Letzte Woche
0
0
Letzter Monat
0
0
geprüft am 14.05.2024