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

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Titel: Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments
Autor(en): Richter, David
Moraga, Ignacio
Winkelmann, Hauke
Birkholz, Oliver
Wilmes, Stephan
Schulte, Markos
Kraich, Michael
Kenneweg, Hella
Beutel, Oliver
Selenschik, Philipp
Paterok, Dirk
Gavutis, Martynas
Schmidt, Thomas
Garcia, K. Christopher
Müller, Thomas D.
Piehler, Jacob
Zusammenfassung: 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
Bibliografische Angaben: Nature Communications 8:15976 (2017). Springer Nature
URL: https://repositorium.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018043016999
Schlagworte: Type II Interleukin-4 receptor; re-association; plasma membrane; microcompartments
Erscheinungsdatum: 30-Apr-2018
Enthalten in den Sammlungen:FB05 - Hochschulschriften
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