DC Element | Wert | Sprache |
dc.contributor.author | You, Changjiang | |
dc.contributor.author | Marquez-Lago, Tatiana T. | |
dc.contributor.author | Richter, Christian Paolo | |
dc.contributor.author | Wilmes, Stephan | |
dc.contributor.author | Moraga, Ignacio | |
dc.contributor.author | Garcia, K. Christopher | |
dc.contributor.author | Leier, Andre | |
dc.contributor.author | Piehler, Jacob | |
dc.date.accessioned | 2021-12-23T16:20:35Z | - |
dc.date.available | 2021-12-23T16:20:35Z | - |
dc.date.issued | 2016 | |
dc.identifier.issn | 23752548 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/13514 | - |
dc.description.abstract | The interaction dynamics of signaling complexes is emerging as a key determinant that regulates the specificity of cellular responses. We present a combined experimental and computational study that quantifies the consequences of plasma membrane microcompartmentalization for the dynamics of type I interferon receptor complexes. By using long-term dual-color quantum dot (QD) tracking, we found that the lifetime of individual ligand-induced receptor heterodimers depends on the integrity of the membrane skeleton (MSK), which also proved important for efficient downstream signaling. By pair correlation tracking and localization microscopy as well as by fast QD tracking, we identified a secondary confinement within similar to 300-nm-sized zones. A quantitative spatial stochastic diffusion-reaction model, entirely parameterized on the basis of experimental data, predicts that transient receptor confinement by the MSK meshwork allows for rapid reassociation of dissociated receptor dimers. Moreover, the experimentally observed apparent stabilization of receptor dimers in the plasma membrane was reproduced by simulations of a refined, hierarchical compartment model. Our simulations further revealed that the two-dimensional association rate constant is a key parameter for controlling the extent of MSK-mediated stabilization of protein complexes, thus ensuring the specificity of this effect. Together, experimental evidence and simulations support the hypothesis that passive receptor confinement by MSK-based microcompartmentalization promotes maintenance of signaling complexes in the plasma membrane. | |
dc.description.sponsorship | Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [SFB 944]; European CommunityEuropean Commission [223608]; Cabinet Office of Japan; Isaac Newton Institute for Mathematical Sciences through EPSRCUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/K032208/1]; Mather's Foundation; HHMIHoward Hughes Medical Institute; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1-AI51321]; EPSRCUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/K032208/1] Funding Source: UKRI; Engineering and Physical Sciences Research CouncilUK Research & Innovation (UKRI)Engineering & Physical Sciences Research Council (EPSRC) [EP/K032208/1] Funding Source: researchfish; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy & Infectious Diseases (NIAID) [R01AI051321] Funding Source: NIH RePORTER; C.Y., C.P.R., S.W., and J.P. were supported by grants (to J.P.) from the Deutsche Forschungsgemeinschaft (SFB 944) and by the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 223608 (IFNaction). T.T.M.-L. and A.L. were supported by funding from the Cabinet Office of Japan. T.T.M.-L. and A.L. would also like to thank the Isaac Newton Institute for Mathematical Sciences for support through EPSRC grant number EP/K032208/1. K.C.G. was funded by the Mather's Foundation, HHMI, and NIH RO1-AI51321. | |
dc.language.iso | en | |
dc.publisher | AMER ASSOC ADVANCEMENT SCIENCE | |
dc.relation.ispartof | SCIENCE ADVANCES | |
dc.subject | DIFFUSION | |
dc.subject | I INTERFERON-RECEPTOR | |
dc.subject | IMAGE CORRELATION SPECTROSCOPY | |
dc.subject | LIVING CELLS | |
dc.subject | LOCALIZATION MICROSCOPY | |
dc.subject | Multidisciplinary Sciences | |
dc.subject | POLYMER-SUPPORTED MEMBRANES | |
dc.subject | PROTEIN COMPLEXES | |
dc.subject | QUANTUM-DOT | |
dc.subject | Science & Technology - Other Topics | |
dc.subject | SINGLE-MOLECULE TRACKING | |
dc.subject | SPATIAL-ORGANIZATION | |
dc.title | Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling | |
dc.type | journal article | |
dc.identifier.doi | 10.1126/sciadv.1600452 | |
dc.identifier.isi | ISI:000391268800004 | |
dc.description.volume | 2 | |
dc.description.issue | 12 | |
dc.contributor.orcid | 0000-0002-7839-6397 | |
dc.contributor.orcid | 0000-0001-9909-0701 | |
dc.contributor.orcid | 0000-0002-2647-2693 | |
dc.contributor.orcid | 0000-0002-4112-710X | |
dc.contributor.researcherid | L-3901-2014 | |
dc.publisher.place | 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA | |
dcterms.isPartOf.abbreviation | Sci. Adv. | |
dcterms.oaStatus | Green Published, Green Submitted, gold | |
crisitem.author.dept | Sonderforschungsbereich 944: Physiologie und Dynamik zellulärer Mikrokompartimente | - |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | organisation19 | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-7839-6397 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | FB 05 - Biologie/Chemie | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.grandparentorg | Universität Osnabrück | - |
crisitem.author.netid | YoCh745 | - |
crisitem.author.netid | PiJa938 | - |