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Mechanistic mathematical model of polarity in yeast

The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a dif...

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Detalles Bibliográficos
Autores principales: Savage, Natasha S., Layton, Anita T., Lew, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350562/
https://www.ncbi.nlm.nih.gov/pubmed/22438587
http://dx.doi.org/10.1091/mbc.E11-10-0837
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author Savage, Natasha S.
Layton, Anita T.
Lew, Daniel J.
author_facet Savage, Natasha S.
Layton, Anita T.
Lew, Daniel J.
author_sort Savage, Natasha S.
collection PubMed
description The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a diffusion-based system, and the other involving actin-directed trafficking of Cdc42p on vesicles. F-actin (and hence directed vesicle traffic) speeds fluorescence recovery of Cdc42p after photobleaching, suggesting that vesicle traffic of Cdc42p contributes to polarization. We present a mathematical modeling framework that combines previously developed mechanistic reaction-diffusion and vesicle-trafficking models. Surprisingly, the combined model recapitulated the observed effect of vesicle traffic on Cdc42p dynamics even when the vesicles did not carry significant amounts of Cdc42p. Vesicle traffic reduced the concentration of Cdc42p at the front, so that fluorescence recovery mediated by Cdc42p flux from the cytoplasm took less time to replenish the bleached pool. Simulations in which Cdc42p was concentrated into vesicles or depleted from vesicles yielded almost identical predictions, because Cdc42p flux from the cytoplasm was dominant. These findings indicate that vesicle-mediated delivery of Cdc42p is not required to explain the observed Cdc42p dynamics, and raise the question of whether such Cdc42p traffic actually contributes to polarity establishment.
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spelling pubmed-33505622012-07-30 Mechanistic mathematical model of polarity in yeast Savage, Natasha S. Layton, Anita T. Lew, Daniel J. Mol Biol Cell Articles The establishment of cell polarity involves positive-feedback mechanisms that concentrate polarity regulators, including the conserved GTPase Cdc42p, at the “front” of the polarized cell. Previous studies in yeast suggested the presence of two parallel positive-feedback loops, one operating as a diffusion-based system, and the other involving actin-directed trafficking of Cdc42p on vesicles. F-actin (and hence directed vesicle traffic) speeds fluorescence recovery of Cdc42p after photobleaching, suggesting that vesicle traffic of Cdc42p contributes to polarization. We present a mathematical modeling framework that combines previously developed mechanistic reaction-diffusion and vesicle-trafficking models. Surprisingly, the combined model recapitulated the observed effect of vesicle traffic on Cdc42p dynamics even when the vesicles did not carry significant amounts of Cdc42p. Vesicle traffic reduced the concentration of Cdc42p at the front, so that fluorescence recovery mediated by Cdc42p flux from the cytoplasm took less time to replenish the bleached pool. Simulations in which Cdc42p was concentrated into vesicles or depleted from vesicles yielded almost identical predictions, because Cdc42p flux from the cytoplasm was dominant. These findings indicate that vesicle-mediated delivery of Cdc42p is not required to explain the observed Cdc42p dynamics, and raise the question of whether such Cdc42p traffic actually contributes to polarity establishment. The American Society for Cell Biology 2012-05-15 /pmc/articles/PMC3350562/ /pubmed/22438587 http://dx.doi.org/10.1091/mbc.E11-10-0837 Text en © 2012 Savage et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Savage, Natasha S.
Layton, Anita T.
Lew, Daniel J.
Mechanistic mathematical model of polarity in yeast
title Mechanistic mathematical model of polarity in yeast
title_full Mechanistic mathematical model of polarity in yeast
title_fullStr Mechanistic mathematical model of polarity in yeast
title_full_unstemmed Mechanistic mathematical model of polarity in yeast
title_short Mechanistic mathematical model of polarity in yeast
title_sort mechanistic mathematical model of polarity in yeast
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350562/
https://www.ncbi.nlm.nih.gov/pubmed/22438587
http://dx.doi.org/10.1091/mbc.E11-10-0837
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