Disturbance of Sphingolipid Biosynthesis Abrogates the Signaling of Mss4, Phosphatidylinositol-4-phosphate 5-Kinase, in Yeast

Kobayashi, Takafumi; Takematsu, Hiromu; Yamaji, Taiki; Hiramoto, Shinsuke; Kozutsumi, Yasunori

doi:10.1074/jbc.m414138200

Cited by 44 publications

(53 citation statements)

References 57 publications

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“…During myriocin treatment, TORC2 activity is increased, whereas Rom2 activity is decreased. Consistent with this notion, Rom2 localization at the plasma membrane is diminished during myriocin treatment (48). This suggests that cells use the reciprocal regulation of both signaling systems to fine-tune communication on the state of the plasma membrane.…”

Section: Discussionsupporting

confidence: 71%

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Olson

Fröhlich

Christiano

et al. 2015

Journal of Biological Chemistry

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Background: Sphingolipids are synthesized from very long-chain fatty acids and sphingoid bases. Results: Rom2 controls Elo2 phosphorylation to regulate very long-chain fatty acid synthesis. Conclusion: Distinct signaling pathways emanating from the plasma membrane regulate the different branches of sphingolipid synthesis. Significance: Signaling from the plasma membrane regulates a key step in sphingolipid synthesis, required for lipid homeostasis of the plasma membrane.

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Section: Discussionsupporting

confidence: 71%

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Olson

Fröhlich

Christiano

et al. 2015

Journal of Biological Chemistry

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“…Both mutants exhibited ,40% increase in PtdIns(4)P levels and a 30-40% decrease in PtdIns(4,5)P 2 levels (Fig. 5A). [ 3 H]inositol labeling was also carried out to determine if complex sphingolipid synthesis was perturbed, as previous studies have suggested that phosphatidylinositol phosphate levels are linked to complex sphingolipid levels (Audhya et al, 2004;Kobayashi et al, 2005;Bultynck et al, 2006;Daquinag et al, 2007;Berchtold et al, 2012). Using inositol labeling, similar results were observed with respect to increased PtdIns(4)P levels and reduced PtdIns(4,5)P 2 levels in the mss4 mutants.…”

Section: Induction Of the Flo11p Cell Adhesion Flocculin Is Reduced Isupporting

confidence: 52%

“…Mss4p is essential for cell viability and cells expressing kinase defective mutants are not viable (Kobayashi et al, 2005;Ling et al, 2012). Cells expressing the mss4-f12 mutant as the sole MSS4 copy were viable, suggesting that this mutant retained catalytic activity.…”

Section: Induction Of the Flo11p Cell Adhesion Flocculin Is Reduced Imentioning

confidence: 99%

“…For example, Slm1p and Slm2p, both PH domain containing PtdIns(4,5)P 2 -binding proteins, interact with TORCs (Audhya et al, 2004;Fadri et al, 2005;Berchtold et al, 2012). Mss4p mediated PtdIns(4,5)P 2 production, Slm1p/Slm2p and Tor kinases are also important for sphingolipid signaling (Audhya et al, 2004;Kobayashi et al, 2005;Bultynck et al, 2006;Daquinag et al, 2007;Roelants et al, 2011;Berchtold et al, 2012;Liu et al, 2012). Starved yeast cells respond to the addition of glucose or ergosterol, the major sterol of S. cerevisiae, by rapid changes in PIPs (Dahl and Dahl, 1985;Kaibuchi et al, 1986;Frascotti et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

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Phosphoinositide-bis-phosphate is required for Saccharomyces cerevisiae invasive growth

Guillas

Vernay

Vitagliano

et al. 2013

Journal of Cell Science

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SummaryPhosphatidylinositol phosphates are important regulators of processes such as the cytoskeleton organization, membrane trafficking and gene transcription, which are all crucial for polarized cell growth. In particular, phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P 2 ] has essential roles in polarized growth as well as in cellular responses to stress. In the yeast Saccharomyces cerevisiae, the sole phosphatidylinositol-4-phosphate 5-kinase (PI4P5K) Mss4p is essential for generating plasma membrane PtdIns(4,5)P 2 . Here, we show that Mss4p is required for yeast invasive growth in low-nutrient conditions. We isolated specific mss4 mutants that were defective in cell elongation, induction of the Flo11p flocculin, adhesion and cell wall integrity. We show that mss4-f12 cells have reduced plasma membrane PtdIns(4,5)P 2 levels as well as a defect in its polarized distribution, yet Mss4-f12p is catalytically active in vitro. In addition, the Mss4-f12 protein was defective in localizing to the plasma membrane. Furthermore, addition of cAMP, but not an activated MAPKKK allele, partially restored the invasive growth defect of mss4-f12 cells. Taken together, our results indicate that plasma membrane PtdIns(4,5)P 2 is crucial for yeast invasive growth and suggest that this phospholipid functions upstream of the cAMP-dependent protein kinase A signaling pathway.

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“…These signaling events are mediated by PtdIns(4,5)P 2 -binding proteins (33)(34)(35). A recent study found that the plasma membrane localization of Mss4 is disturbed in ⌬csg2 cells (36), suggesting that accumulation of IPC-C or loss of MIPC causes mislocalization of Mss4.…”

Section: Discussionmentioning

confidence: 99%

Regulation of the Transport and Protein Levels of the Inositol Phosphorylceramide Mannosyltransferases Csg1 and Csh1 by the Ca2+-binding Protein Csg2

Uemura

Kihara

Iwaki

et al. 2007

Journal of Biological Chemistry

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Complex sphingolipids in yeast are known to function in cellular adaptation to environmental changes. One of the yeast complex sphingolipids, mannosylinositol phosphorylceramide (MIPC), is produced by the redundant inositol phosphorylceramide (IPC) mannosyltransferases Csg1 and Csh1. The Ca 2؉ -binding protein Csg2 can form a complex with either Csg1 or Csh1 and is considered to act as a regulatory subunit. However, the role of Csg2 in MIPC synthesis has remained unclear. In this study, we found that Csg1 and Csh1 are N-glycosylated with core-type and mannan-type structures, respectively. Further identification of the glycosylated residues suggests that both Csg1 and Csh1 exhibit membrane topology with their C termini in the cytosol and their mannosyltransferase domains in the lumen. After complexing with Csg2, both Csg1 and Csh1 function in the Golgi, and then are delivered to the vacuole for degradation. However, uncomplexed Csh1 cannot exit from the endoplasmic reticulum. We also demonstrated that Ca 2؉ stimulates IPC-to-MIPC conversion, because of a Csg2-dependent increase in Csg1 levels. Thus, Csg2 has several regulatory functions for Csg1 and Csh1, including stability, transport, and gene expression.

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Disturbance of Sphingolipid Biosynthesis Abrogates the Signaling of Mss4, Phosphatidylinositol-4-phosphate 5-Kinase, in Yeast

Cited by 44 publications

References 57 publications

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Rom2-dependent Phosphorylation of Elo2 Controls the Abundance of Very Long-chain Fatty Acids

Phosphoinositide-bis-phosphate is required for Saccharomyces cerevisiae invasive growth

Regulation of the Transport and Protein Levels of the Inositol Phosphorylceramide Mannosyltransferases Csg1 and Csh1 by the Ca2+-binding Protein Csg2

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