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Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor
Integrating signals from multiple receptors allows cells to interpret the physiological context in which a signal is received. Here we describe a mechanism for receptor crosstalk in which receptor-induced increases in actin dynamics lower the threshold for signalling by another receptor. We show tha...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Pub. Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327415/ https://www.ncbi.nlm.nih.gov/pubmed/25644899 http://dx.doi.org/10.1038/ncomms7168 |
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author | Freeman, Spencer A. Jaumouillé, Valentin Choi, Kate Hsu, Brian E. Wong, Harikesh S. Abraham, Libin Graves, Marcia L. Coombs, Daniel Roskelley, Calvin D. Das, Raibatak Grinstein, Sergio Gold, Michael R. |
author_facet | Freeman, Spencer A. Jaumouillé, Valentin Choi, Kate Hsu, Brian E. Wong, Harikesh S. Abraham, Libin Graves, Marcia L. Coombs, Daniel Roskelley, Calvin D. Das, Raibatak Grinstein, Sergio Gold, Michael R. |
author_sort | Freeman, Spencer A. |
collection | PubMed |
description | Integrating signals from multiple receptors allows cells to interpret the physiological context in which a signal is received. Here we describe a mechanism for receptor crosstalk in which receptor-induced increases in actin dynamics lower the threshold for signalling by another receptor. We show that the Toll-like receptor ligands lipopolysaccharide and CpG DNA, which are conserved microbial molecules, enhance signalling by the B-cell antigen receptor (BCR) by activating the actin-severing protein cofilin. Single-particle tracking reveals that increased severing of actin filaments reduces the spatial confinement of the BCR within the plasma membrane and increases BCR mobility. This allows more frequent collisions between BCRs and greater signalling in response to low densities of membrane-bound antigen. These findings implicate actin dynamics as a means of tuning receptor signalling and as a mechanism by which B cells distinguish inert antigens from those that are accompanied by indicators of microbial infection. |
format | Online Article Text |
id | pubmed-4327415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Pub. Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-43274152015-02-24 Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor Freeman, Spencer A. Jaumouillé, Valentin Choi, Kate Hsu, Brian E. Wong, Harikesh S. Abraham, Libin Graves, Marcia L. Coombs, Daniel Roskelley, Calvin D. Das, Raibatak Grinstein, Sergio Gold, Michael R. Nat Commun Article Integrating signals from multiple receptors allows cells to interpret the physiological context in which a signal is received. Here we describe a mechanism for receptor crosstalk in which receptor-induced increases in actin dynamics lower the threshold for signalling by another receptor. We show that the Toll-like receptor ligands lipopolysaccharide and CpG DNA, which are conserved microbial molecules, enhance signalling by the B-cell antigen receptor (BCR) by activating the actin-severing protein cofilin. Single-particle tracking reveals that increased severing of actin filaments reduces the spatial confinement of the BCR within the plasma membrane and increases BCR mobility. This allows more frequent collisions between BCRs and greater signalling in response to low densities of membrane-bound antigen. These findings implicate actin dynamics as a means of tuning receptor signalling and as a mechanism by which B cells distinguish inert antigens from those that are accompanied by indicators of microbial infection. Nature Pub. Group 2015-02-03 /pmc/articles/PMC4327415/ /pubmed/25644899 http://dx.doi.org/10.1038/ncomms7168 Text en Copyright © 2015, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Freeman, Spencer A. Jaumouillé, Valentin Choi, Kate Hsu, Brian E. Wong, Harikesh S. Abraham, Libin Graves, Marcia L. Coombs, Daniel Roskelley, Calvin D. Das, Raibatak Grinstein, Sergio Gold, Michael R. Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
title | Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
title_full | Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
title_fullStr | Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
title_full_unstemmed | Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
title_short | Toll-like receptor ligands sensitize B-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
title_sort | toll-like receptor ligands sensitize b-cell receptor signalling by reducing actin-dependent spatial confinement of the receptor |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327415/ https://www.ncbi.nlm.nih.gov/pubmed/25644899 http://dx.doi.org/10.1038/ncomms7168 |
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