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A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast

Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the...

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Autores principales: García, Raúl, Bravo, Enrique, Diez-Muñiz, Sonia, Nombela, Cesar, Rodríguez-Peña, Jose M., Arroyo, Javier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515849/
https://www.ncbi.nlm.nih.gov/pubmed/28720901
http://dx.doi.org/10.1038/s41598-017-06001-9
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author García, Raúl
Bravo, Enrique
Diez-Muñiz, Sonia
Nombela, Cesar
Rodríguez-Peña, Jose M.
Arroyo, Javier
author_facet García, Raúl
Bravo, Enrique
Diez-Muñiz, Sonia
Nombela, Cesar
Rodríguez-Peña, Jose M.
Arroyo, Javier
author_sort García, Raúl
collection PubMed
description Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group. Moreover, cell wall stress mediated by inhibition of β-1,3-glucan synthesis, but not by other cell wall interfering compounds, negatively regulated PKA signaling as indicated by the nuclear localisation of Msn2, cellular glycogen accumulation, a decrease of intracellular cAMP levels and a severe decrease in both the activation of the small GTPase Ras2 and the phosphorylation of known substrates of PKA. All these effects relied on the plasma membrane-spanning sensor of the CWI pathway Wsc1. In addition, caspofungin induced a reduction in the cytosolic pH, which was dependent on the extracellular region of Wsc1. Therefore, alterations of the β-1,3-glucan network in the fungal cell wall, induce, through Wsc1, the activation of the CWI pathway and parallel inhibition of PKA signaling.
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spelling pubmed-55158492017-07-19 A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast García, Raúl Bravo, Enrique Diez-Muñiz, Sonia Nombela, Cesar Rodríguez-Peña, Jose M. Arroyo, Javier Sci Rep Article Fungal cells trigger adaptive mechanisms to survive in situations that compromise cell wall integrity. We show here that the global transcriptional response elicited by inhibition of the synthesis of β-1,3-glucan by caspofungin, encompasses a set of genes that are dependent on Slt2, the MAPK of the Cell Wall Integrity (CWI) pathway, and a broad group of genes regulated independently of Slt2. Genes negatively regulated by the cyclic AMP/Protein Kinase A (PKA) signaling pathway were overrepresented in the latter group. Moreover, cell wall stress mediated by inhibition of β-1,3-glucan synthesis, but not by other cell wall interfering compounds, negatively regulated PKA signaling as indicated by the nuclear localisation of Msn2, cellular glycogen accumulation, a decrease of intracellular cAMP levels and a severe decrease in both the activation of the small GTPase Ras2 and the phosphorylation of known substrates of PKA. All these effects relied on the plasma membrane-spanning sensor of the CWI pathway Wsc1. In addition, caspofungin induced a reduction in the cytosolic pH, which was dependent on the extracellular region of Wsc1. Therefore, alterations of the β-1,3-glucan network in the fungal cell wall, induce, through Wsc1, the activation of the CWI pathway and parallel inhibition of PKA signaling. Nature Publishing Group UK 2017-07-18 /pmc/articles/PMC5515849/ /pubmed/28720901 http://dx.doi.org/10.1038/s41598-017-06001-9 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
García, Raúl
Bravo, Enrique
Diez-Muñiz, Sonia
Nombela, Cesar
Rodríguez-Peña, Jose M.
Arroyo, Javier
A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
title A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
title_full A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
title_fullStr A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
title_full_unstemmed A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
title_short A novel connection between the Cell Wall Integrity and the PKA pathways regulates cell wall stress response in yeast
title_sort novel connection between the cell wall integrity and the pka pathways regulates cell wall stress response in yeast
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5515849/
https://www.ncbi.nlm.nih.gov/pubmed/28720901
http://dx.doi.org/10.1038/s41598-017-06001-9
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