Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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
_version_ 1783449010241011712
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
work_keys_str_mv AT sørensendannymollerup thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT holenhenrikwaldal thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT pedersenjespertorbøl thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT martenshellejuel thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT silvestrodaniele thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT stanchevlyubomirdimitrov thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT costasararute thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT guntherpomorskithomas thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT lopezmarquesrosalaura thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT palmgrenmichael thep5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT sørensendannymollerup p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT holenhenrikwaldal p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT pedersenjespertorbøl p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT martenshellejuel p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT silvestrodaniele p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT stanchevlyubomirdimitrov p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT costasararute p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT guntherpomorskithomas p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT lopezmarquesrosalaura p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis
AT palmgrenmichael p5aatpasespf1pisstimulatedbyphosphatidylinositol4phosphateandinfluencescellularsterolhomeostasis