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Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport

Arsenic is an environmental toxin that exists mainly as pentavalent arsenate and trivalent arsenite. Both forms activate the yeast SAPK Hog1 but with different consequences. We describe a mechanism by which cells distinguish between these arsenicals through one-step metabolism to differentially regu...

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Autores principales: Lee, Jongmin, Levin, David E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932518/
https://www.ncbi.nlm.nih.gov/pubmed/35139143
http://dx.doi.org/10.1083/jcb.202109034
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author Lee, Jongmin
Levin, David E.
author_facet Lee, Jongmin
Levin, David E.
author_sort Lee, Jongmin
collection PubMed
description Arsenic is an environmental toxin that exists mainly as pentavalent arsenate and trivalent arsenite. Both forms activate the yeast SAPK Hog1 but with different consequences. We describe a mechanism by which cells distinguish between these arsenicals through one-step metabolism to differentially regulate the bidirectional glycerol channel Fps1, an adventitious port for arsenite. Cells exposed to arsenate reduce it to thiol-reactive arsenite, which modifies a set of cysteine residues in target proteins, whereas cells exposed to arsenite metabolize it to methylarsenite, which modifies an additional set of cysteine residues. Hog1 becomes arsenylated, which prevents it from closing Fps1. However, this block is overcome in cells exposed to arsenite through methylarsenylation of Acr3, an arsenite efflux pump that we found also regulates Fps1 directly. This adaptation allows cells to restrict arsenite entry through Fps1 and also allows its exit when produced from arsenate exposure. These results have broad implications for understanding how SAPKs activated by diverse stressors can drive stress-specific outputs.
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spelling pubmed-89325182022-09-07 Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport Lee, Jongmin Levin, David E. J Cell Biol Article Arsenic is an environmental toxin that exists mainly as pentavalent arsenate and trivalent arsenite. Both forms activate the yeast SAPK Hog1 but with different consequences. We describe a mechanism by which cells distinguish between these arsenicals through one-step metabolism to differentially regulate the bidirectional glycerol channel Fps1, an adventitious port for arsenite. Cells exposed to arsenate reduce it to thiol-reactive arsenite, which modifies a set of cysteine residues in target proteins, whereas cells exposed to arsenite metabolize it to methylarsenite, which modifies an additional set of cysteine residues. Hog1 becomes arsenylated, which prevents it from closing Fps1. However, this block is overcome in cells exposed to arsenite through methylarsenylation of Acr3, an arsenite efflux pump that we found also regulates Fps1 directly. This adaptation allows cells to restrict arsenite entry through Fps1 and also allows its exit when produced from arsenate exposure. These results have broad implications for understanding how SAPKs activated by diverse stressors can drive stress-specific outputs. Rockefeller University Press 2022-02-09 /pmc/articles/PMC8932518/ /pubmed/35139143 http://dx.doi.org/10.1083/jcb.202109034 Text en © 2022 Lee and Levin https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Lee, Jongmin
Levin, David E.
Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport
title Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport
title_full Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport
title_fullStr Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport
title_full_unstemmed Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport
title_short Differential metabolism of arsenicals regulates Fps1-mediated arsenite transport
title_sort differential metabolism of arsenicals regulates fps1-mediated arsenite transport
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8932518/
https://www.ncbi.nlm.nih.gov/pubmed/35139143
http://dx.doi.org/10.1083/jcb.202109034
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