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TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites
In our proteome-wide screen, Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of the TOR complex 2 (TORC2)–dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins lo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232965/ https://www.ncbi.nlm.nih.gov/pubmed/29927351 http://dx.doi.org/10.1091/mbc.E18-04-0229 |
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author | Roelants, Françoise M. Chauhan, Neha Muir, Alexander Davis, Jameson C. Menon, Anant K. Levine, Timothy P. Thorner, Jeremy |
author_facet | Roelants, Françoise M. Chauhan, Neha Muir, Alexander Davis, Jameson C. Menon, Anant K. Levine, Timothy P. Thorner, Jeremy |
author_sort | Roelants, Françoise M. |
collection | PubMed |
description | In our proteome-wide screen, Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of the TOR complex 2 (TORC2)–dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins located at plasma membrane (PM)–endoplasmic reticulum (ER) contact sites. Here we document that Ysp2 and its paralogue Lam4/Ltc3 are authentic Ypk1 substrates in vivo and show using genetic and biochemical criteria that Ypk1-mediated phosphorylation inhibits the ability of these proteins to promote retrograde transport of sterols from the PM to the ER. Furthermore, we provide evidence that a change in PM sterol homeostasis promotes cell survival under membrane-perturbing conditions known to activate TORC2-Ypk1 signaling. These observations define the underlying molecular basis of a new regulatory mechanism for cellular response to plasma membrane stress. |
format | Online Article Text |
id | pubmed-6232965 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62329652018-11-20 TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites Roelants, Françoise M. Chauhan, Neha Muir, Alexander Davis, Jameson C. Menon, Anant K. Levine, Timothy P. Thorner, Jeremy Mol Biol Cell Articles In our proteome-wide screen, Ysp2 (also known as Lam2/Ltc4) was identified as a likely physiologically relevant target of the TOR complex 2 (TORC2)–dependent protein kinase Ypk1 in the yeast Saccharomyces cerevisiae. Ysp2 was subsequently shown to be one of a new family of sterol-binding proteins located at plasma membrane (PM)–endoplasmic reticulum (ER) contact sites. Here we document that Ysp2 and its paralogue Lam4/Ltc3 are authentic Ypk1 substrates in vivo and show using genetic and biochemical criteria that Ypk1-mediated phosphorylation inhibits the ability of these proteins to promote retrograde transport of sterols from the PM to the ER. Furthermore, we provide evidence that a change in PM sterol homeostasis promotes cell survival under membrane-perturbing conditions known to activate TORC2-Ypk1 signaling. These observations define the underlying molecular basis of a new regulatory mechanism for cellular response to plasma membrane stress. The American Society for Cell Biology 2018-08-15 /pmc/articles/PMC6232965/ /pubmed/29927351 http://dx.doi.org/10.1091/mbc.E18-04-0229 Text en © 2018 Roelants et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Roelants, Françoise M. Chauhan, Neha Muir, Alexander Davis, Jameson C. Menon, Anant K. Levine, Timothy P. Thorner, Jeremy TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
title | TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
title_full | TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
title_fullStr | TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
title_full_unstemmed | TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
title_short | TOR complex 2–regulated protein kinase Ypk1 controls sterol distribution by inhibiting StARkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
title_sort | tor complex 2–regulated protein kinase ypk1 controls sterol distribution by inhibiting starkin domain–containing proteins located at plasma membrane–endoplasmic reticulum contact sites |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232965/ https://www.ncbi.nlm.nih.gov/pubmed/29927351 http://dx.doi.org/10.1091/mbc.E18-04-0229 |
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