%0 Journal Article %1 Richter:2017:Nat-Commun:28706306 %A Richter, D %A Moraga, I %A Winkelmann, H %A Birkholz, O %A Wilmes, S %A Schulte, M %A Kraich, M %A Kenneweg, H %A Beutel, O %A Selenschik, P %A Paterok, D %A Gavutis, M %A Schmidt, T %A Garcia, K C %A Müller, T D %A Piehler, J %D 2017 %J Nat Commun %K myown %P 15976-15976 %R 10.1038/ncomms15976 %T Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments %U https://www.ncbi.nlm.nih.gov/pubmed/28706306 %V 8 %X 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.

@article{Richter:2017:Nat-Commun:28706306, 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.}, added-at = {2017-07-18T10:22:16.000+0200}, author = {Richter, D and Moraga, I and Winkelmann, H and Birkholz, O and Wilmes, S and Schulte, M and Kraich, M and Kenneweg, H and Beutel, O and Selenschik, P and Paterok, D and Gavutis, M and Schmidt, T and Garcia, K C and M{\"u}ller, T D and Piehler, J}, biburl = {https://www.bibsonomy.org/bibtex/23ee57e33b026693d7c2e241a8e7dac28/tdmueller}, description = {Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments. - PubMed - NCBI}, doi = {10.1038/ncomms15976}, interhash = {adcff26dbfc8cd1329fb91677251e8fb}, intrahash = {3ee57e33b026693d7c2e241a8e7dac28}, journal = {Nat Commun}, keywords = {myown}, month = jul, pages = {15976-15976}, pmid = {28706306}, timestamp = {2017-07-18T10:22:16.000+0200}, title = {Ligand-induced type II interleukin-4 receptor dimers are sustained by rapid re-association within plasma membrane microcompartments}, url = {https://www.ncbi.nlm.nih.gov/pubmed/28706306}, volume = 8, year = 2017 }