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Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5

Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanica...

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Autores principales: van Drogen, Frank, Mishra, Ranjan, Rudolf, Fabian, Walczak, Michal J., Lee, Sung Sik, Reiter, Wolfgang, Hegemann, Björn, Pelet, Serge, Dohnal, Ilse, Binolfi, Andres, Yudina, Zinaida, Selenko, Philipp, Wider, Gerhard, Ammerer, Gustav, Peter, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719448/
https://www.ncbi.nlm.nih.gov/pubmed/31315942
http://dx.doi.org/10.1083/jcb.201808161
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author van Drogen, Frank
Mishra, Ranjan
Rudolf, Fabian
Walczak, Michal J.
Lee, Sung Sik
Reiter, Wolfgang
Hegemann, Björn
Pelet, Serge
Dohnal, Ilse
Binolfi, Andres
Yudina, Zinaida
Selenko, Philipp
Wider, Gerhard
Ammerer, Gustav
Peter, Matthias
author_facet van Drogen, Frank
Mishra, Ranjan
Rudolf, Fabian
Walczak, Michal J.
Lee, Sung Sik
Reiter, Wolfgang
Hegemann, Björn
Pelet, Serge
Dohnal, Ilse
Binolfi, Andres
Yudina, Zinaida
Selenko, Philipp
Wider, Gerhard
Ammerer, Gustav
Peter, Matthias
author_sort van Drogen, Frank
collection PubMed
description Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell–cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell–cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress–triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell–cell fusion during mating.
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spelling pubmed-67194482020-03-02 Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5 van Drogen, Frank Mishra, Ranjan Rudolf, Fabian Walczak, Michal J. Lee, Sung Sik Reiter, Wolfgang Hegemann, Björn Pelet, Serge Dohnal, Ilse Binolfi, Andres Yudina, Zinaida Selenko, Philipp Wider, Gerhard Ammerer, Gustav Peter, Matthias J Cell Biol Research Articles Cells continuously adapt cellular processes by integrating external and internal signals. In yeast, multiple stress signals regulate pheromone signaling to prevent mating under unfavorable conditions. However, the underlying crosstalk mechanisms remain poorly understood. Here, we show that mechanical stress activates Pkc1, which prevents lysis of pheromone-treated cells by inhibiting polarized growth. In vitro Pkc1 phosphorylates conserved residues within the RING-H2 domains of the scaffold proteins Far1 and Ste5, which are also phosphorylated in vivo. Interestingly, Pkc1 triggers dispersal of Ste5 from mating projections upon mechanically induced stress and during cell–cell fusion, leading to inhibition of the MAPK Fus3. Indeed, RING phosphorylation interferes with Ste5 membrane association by preventing binding to the receptor-linked Gβγ protein. Cells expressing nonphosphorylatable Ste5 undergo increased lysis upon mechanical stress and exhibit defects in cell–cell fusion during mating, which is exacerbated by simultaneous expression of nonphosphorylatable Far1. These results uncover a mechanical stress–triggered crosstalk mechanism modulating pheromone signaling, polarized growth, and cell–cell fusion during mating. Rockefeller University Press 2019-09-02 2019-07-17 /pmc/articles/PMC6719448/ /pubmed/31315942 http://dx.doi.org/10.1083/jcb.201808161 Text en © 2019 van Drogen et al. 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 Research Articles
van Drogen, Frank
Mishra, Ranjan
Rudolf, Fabian
Walczak, Michal J.
Lee, Sung Sik
Reiter, Wolfgang
Hegemann, Björn
Pelet, Serge
Dohnal, Ilse
Binolfi, Andres
Yudina, Zinaida
Selenko, Philipp
Wider, Gerhard
Ammerer, Gustav
Peter, Matthias
Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_full Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_fullStr Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_full_unstemmed Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_short Mechanical stress impairs pheromone signaling via Pkc1-mediated regulation of the MAPK scaffold Ste5
title_sort mechanical stress impairs pheromone signaling via pkc1-mediated regulation of the mapk scaffold ste5
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719448/
https://www.ncbi.nlm.nih.gov/pubmed/31315942
http://dx.doi.org/10.1083/jcb.201808161
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