Cargando…
Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling
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 i...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135388/ https://www.ncbi.nlm.nih.gov/pubmed/27957535 http://dx.doi.org/10.1126/sciadv.1600452 |
_version_ | 1782471578656702464 |
---|---|
author | You, Changjiang Marquez-Lago, Tatiana T. Richter, Christian Paolo Wilmes, Stephan Moraga, Ignacio Garcia, K. Christopher Leier, André Piehler, Jacob |
author_facet | You, Changjiang Marquez-Lago, Tatiana T. Richter, Christian Paolo Wilmes, Stephan Moraga, Ignacio Garcia, K. Christopher Leier, André Piehler, Jacob |
author_sort | You, Changjiang |
collection | PubMed |
description | 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 ~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. |
format | Online Article Text |
id | pubmed-5135388 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51353882016-12-12 Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling You, Changjiang Marquez-Lago, Tatiana T. Richter, Christian Paolo Wilmes, Stephan Moraga, Ignacio Garcia, K. Christopher Leier, André Piehler, Jacob Sci Adv Research Articles 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 ~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. American Association for the Advancement of Science 2016-12-02 /pmc/articles/PMC5135388/ /pubmed/27957535 http://dx.doi.org/10.1126/sciadv.1600452 Text en Copyright © 2016, The Authors http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles You, Changjiang Marquez-Lago, Tatiana T. Richter, Christian Paolo Wilmes, Stephan Moraga, Ignacio Garcia, K. Christopher Leier, André Piehler, Jacob Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
title | Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
title_full | Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
title_fullStr | Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
title_full_unstemmed | Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
title_short | Receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
title_sort | receptor dimer stabilization by hierarchical plasma membrane microcompartments regulates cytokine signaling |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5135388/ https://www.ncbi.nlm.nih.gov/pubmed/27957535 http://dx.doi.org/10.1126/sciadv.1600452 |
work_keys_str_mv | AT youchangjiang receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT marquezlagotatianat receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT richterchristianpaolo receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT wilmesstephan receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT moragaignacio receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT garciakchristopher receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT leierandre receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling AT piehlerjacob receptordimerstabilizationbyhierarchicalplasmamembranemicrocompartmentsregulatescytokinesignaling |