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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...

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Autores principales: Roelants, Françoise M., Chauhan, Neha, Muir, Alexander, Davis, Jameson C., Menon, Anant K., Levine, Timothy P., Thorner, Jeremy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2018
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.
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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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