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Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks
Detecting relative rather than absolute changes in extracellular signals enables cells to make decisions in constantly fluctuating environments. It is currently not well understood how mammalian signaling networks store the memories of past stimuli and subsequently use them to compute relative signa...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046471/ https://www.ncbi.nlm.nih.gov/pubmed/31961323 http://dx.doi.org/10.7554/eLife.50342 |
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author | Lyashenko, Eugenia Niepel, Mario Dixit, Purushottam D Lim, Sang Kyun Sorger, Peter K Vitkup, Dennis |
author_facet | Lyashenko, Eugenia Niepel, Mario Dixit, Purushottam D Lim, Sang Kyun Sorger, Peter K Vitkup, Dennis |
author_sort | Lyashenko, Eugenia |
collection | PubMed |
description | Detecting relative rather than absolute changes in extracellular signals enables cells to make decisions in constantly fluctuating environments. It is currently not well understood how mammalian signaling networks store the memories of past stimuli and subsequently use them to compute relative signals, that is perform fold change detection. Using the growth factor-activated PI3K-Akt signaling pathway, we develop here computational and analytical models, and experimentally validate a novel non-transcriptional mechanism of relative sensing in mammalian cells. This mechanism relies on a new form of cellular memory, where cells effectively encode past stimulation levels in the abundance of cognate receptors on the cell surface. The surface receptor abundance is regulated by background signal-dependent receptor endocytosis and down-regulation. We show the robustness and specificity of relative sensing for two physiologically important ligands, epidermal growth factor (EGF) and hepatocyte growth factor (HGF), and across wide ranges of background stimuli. Our results suggest that similar mechanisms of cell memory and fold change detection may be important in diverse signaling cascades and multiple biological contexts. |
format | Online Article Text |
id | pubmed-7046471 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-70464712020-03-02 Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks Lyashenko, Eugenia Niepel, Mario Dixit, Purushottam D Lim, Sang Kyun Sorger, Peter K Vitkup, Dennis eLife Computational and Systems Biology Detecting relative rather than absolute changes in extracellular signals enables cells to make decisions in constantly fluctuating environments. It is currently not well understood how mammalian signaling networks store the memories of past stimuli and subsequently use them to compute relative signals, that is perform fold change detection. Using the growth factor-activated PI3K-Akt signaling pathway, we develop here computational and analytical models, and experimentally validate a novel non-transcriptional mechanism of relative sensing in mammalian cells. This mechanism relies on a new form of cellular memory, where cells effectively encode past stimulation levels in the abundance of cognate receptors on the cell surface. The surface receptor abundance is regulated by background signal-dependent receptor endocytosis and down-regulation. We show the robustness and specificity of relative sensing for two physiologically important ligands, epidermal growth factor (EGF) and hepatocyte growth factor (HGF), and across wide ranges of background stimuli. Our results suggest that similar mechanisms of cell memory and fold change detection may be important in diverse signaling cascades and multiple biological contexts. eLife Sciences Publications, Ltd 2020-01-21 /pmc/articles/PMC7046471/ /pubmed/31961323 http://dx.doi.org/10.7554/eLife.50342 Text en © 2020, Lyashenko et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Computational and Systems Biology Lyashenko, Eugenia Niepel, Mario Dixit, Purushottam D Lim, Sang Kyun Sorger, Peter K Vitkup, Dennis Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
title | Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
title_full | Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
title_fullStr | Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
title_full_unstemmed | Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
title_short | Receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
title_sort | receptor-based mechanism of relative sensing and cell memory in mammalian signaling networks |
topic | Computational and Systems Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046471/ https://www.ncbi.nlm.nih.gov/pubmed/31961323 http://dx.doi.org/10.7554/eLife.50342 |
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