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Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus
For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane an...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704053/ https://www.ncbi.nlm.nih.gov/pubmed/33196636 http://dx.doi.org/10.1371/journal.pcbi.1008356 |
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author | Ma, Jingwei Do, Myan Le Gros, Mark A. Peskin, Charles S. Larabell, Carolyn A. Mori, Yoichiro Isaacson, Samuel A. |
author_facet | Ma, Jingwei Do, Myan Le Gros, Mark A. Peskin, Charles S. Larabell, Carolyn A. Mori, Yoichiro Isaacson, Samuel A. |
author_sort | Ma, Jingwei |
collection | PubMed |
description | For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane and diffuse throughout the cytosol. Organelle surfaces within human B cells are reconstructed from soft X-ray tomographic images, and modeled as reflecting barriers to the molecules’ diffusion. We show that signal inactivation sharpens signals, reducing variability in the arrival time at the nuclear membrane. Inactivation can also compensate for an observed slowdown in signal propagation induced by the presence of organelle barriers, leading to arrival times at the nuclear membrane that are comparable to models in which the cytosol is treated as an open, empty region. In the limit of strong signal inactivation this is achieved by filtering out molecules that traverse non-geodesic paths. |
format | Online Article Text |
id | pubmed-7704053 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-77040532020-12-08 Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus Ma, Jingwei Do, Myan Le Gros, Mark A. Peskin, Charles S. Larabell, Carolyn A. Mori, Yoichiro Isaacson, Samuel A. PLoS Comput Biol Research Article For a chemical signal to propagate across a cell, it must navigate a tortuous environment involving a variety of organelle barriers. In this work we study mathematical models for a basic chemical signal, the arrival times at the nuclear membrane of proteins that are activated at the cell membrane and diffuse throughout the cytosol. Organelle surfaces within human B cells are reconstructed from soft X-ray tomographic images, and modeled as reflecting barriers to the molecules’ diffusion. We show that signal inactivation sharpens signals, reducing variability in the arrival time at the nuclear membrane. Inactivation can also compensate for an observed slowdown in signal propagation induced by the presence of organelle barriers, leading to arrival times at the nuclear membrane that are comparable to models in which the cytosol is treated as an open, empty region. In the limit of strong signal inactivation this is achieved by filtering out molecules that traverse non-geodesic paths. Public Library of Science 2020-11-16 /pmc/articles/PMC7704053/ /pubmed/33196636 http://dx.doi.org/10.1371/journal.pcbi.1008356 Text en © 2020 Ma et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Ma, Jingwei Do, Myan Le Gros, Mark A. Peskin, Charles S. Larabell, Carolyn A. Mori, Yoichiro Isaacson, Samuel A. Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
title | Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
title_full | Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
title_fullStr | Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
title_full_unstemmed | Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
title_short | Strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
title_sort | strong intracellular signal inactivation produces sharper and more robust signaling from cell membrane to nucleus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704053/ https://www.ncbi.nlm.nih.gov/pubmed/33196636 http://dx.doi.org/10.1371/journal.pcbi.1008356 |
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