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The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis
P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in severe ER stress. However, the function of these ubiquitous membrane proteins, which belong to the P-type ATPase superfamily, is unknown. We purified a functional tagged version of th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724510/ https://www.ncbi.nlm.nih.gov/pubmed/30785834 http://dx.doi.org/10.1091/mbc.E18-06-0365 |
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author | Sørensen, Danny Mollerup Holen, Henrik Waldal Pedersen, Jesper Torbøl Martens, Helle Juel Silvestro, Daniele Stanchev, Lyubomir Dimitrov Costa, Sara Rute Günther Pomorski, Thomas López-Marqués, Rosa Laura Palmgren, Michael |
author_facet | Sørensen, Danny Mollerup Holen, Henrik Waldal Pedersen, Jesper Torbøl Martens, Helle Juel Silvestro, Daniele Stanchev, Lyubomir Dimitrov Costa, Sara Rute Günther Pomorski, Thomas López-Marqués, Rosa Laura Palmgren, Michael |
author_sort | Sørensen, Danny Mollerup |
collection | PubMed |
description | P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in severe ER stress. However, the function of these ubiquitous membrane proteins, which belong to the P-type ATPase superfamily, is unknown. We purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and observed that the ATP hydrolytic activity of the protein is stimulated by phosphatidylinositol 4-phosphate (PI4P). Furthermore, SPF1 exhibited negative genetic interactions with SAC1, encoding a PI4P phosphatase, and with OSH1 to OSH6, encoding Osh proteins, which, when energized by a PI4P gradient, drive export of sterols and lipids from the ER. Deletion of SPF1 resulted in increased sensitivity to inhibitors of sterol production, a marked change in the ergosterol/lanosterol ratio, accumulation of sterols in the plasma membrane, and cytosolic accumulation of lipid bodies. We propose that Spf1p maintains cellular sterol homeostasis by influencing the PI4P-induced and Osh-mediated export of sterols from the ER. |
format | Online Article Text |
id | pubmed-6724510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67245102019-09-04 The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis Sørensen, Danny Mollerup Holen, Henrik Waldal Pedersen, Jesper Torbøl Martens, Helle Juel Silvestro, Daniele Stanchev, Lyubomir Dimitrov Costa, Sara Rute Günther Pomorski, Thomas López-Marqués, Rosa Laura Palmgren, Michael Mol Biol Cell Articles P5A ATPases are expressed in the endoplasmic reticulum (ER) of all eukaryotic cells, and their disruption results in severe ER stress. However, the function of these ubiquitous membrane proteins, which belong to the P-type ATPase superfamily, is unknown. We purified a functional tagged version of the Saccharomyces cerevisiae P5A ATPase Spf1p and observed that the ATP hydrolytic activity of the protein is stimulated by phosphatidylinositol 4-phosphate (PI4P). Furthermore, SPF1 exhibited negative genetic interactions with SAC1, encoding a PI4P phosphatase, and with OSH1 to OSH6, encoding Osh proteins, which, when energized by a PI4P gradient, drive export of sterols and lipids from the ER. Deletion of SPF1 resulted in increased sensitivity to inhibitors of sterol production, a marked change in the ergosterol/lanosterol ratio, accumulation of sterols in the plasma membrane, and cytosolic accumulation of lipid bodies. We propose that Spf1p maintains cellular sterol homeostasis by influencing the PI4P-induced and Osh-mediated export of sterols from the ER. The American Society for Cell Biology 2019-04-15 /pmc/articles/PMC6724510/ /pubmed/30785834 http://dx.doi.org/10.1091/mbc.E18-06-0365 Text en © 2019 Sørensen, Holen, 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 Sørensen, Danny Mollerup Holen, Henrik Waldal Pedersen, Jesper Torbøl Martens, Helle Juel Silvestro, Daniele Stanchev, Lyubomir Dimitrov Costa, Sara Rute Günther Pomorski, Thomas López-Marqués, Rosa Laura Palmgren, Michael The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
title | The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
title_full | The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
title_fullStr | The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
title_full_unstemmed | The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
title_short | The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
title_sort | p5a atpase spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724510/ https://www.ncbi.nlm.nih.gov/pubmed/30785834 http://dx.doi.org/10.1091/mbc.E18-06-0365 |
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