The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis
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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; Pomorski, Thomas Günther; López-Marqués, Rosa Laura; Palmgren, Michael.
I: Molecular Biology of the Cell, Bind 30, Nr. 9, 15.04.2019, s. 1069-1084.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - The P5A ATPase Spf1p is stimulated by phosphatidylinositol 4-phosphate and influences cellular sterol homeostasis
AU - Sørensen, Danny Mollerup
AU - Holen, Henrik Waldal
AU - Pedersen, Jesper Torbøl
AU - Martens, Helle Juel
AU - Silvestro, Daniele
AU - Stanchev, Lyubomir Dimitrov
AU - Costa, Sara Rute
AU - Pomorski, Thomas Günther
AU - López-Marqués, Rosa Laura
AU - Palmgren, Michael
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85064814513&partnerID=8YFLogxK
U2 - 10.1091/mbc.E18-06-0365
DO - 10.1091/mbc.E18-06-0365
M3 - Journal article
C2 - 30785834
AN - SCOPUS:85064814513
VL - 30
SP - 1069
EP - 1084
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
SN - 1059-1524
IS - 9
ER -
ID: 224336803