The Yeast PH Domain Proteins Slm1 and Slm2 Are Targets of Sphingolipid Signaling during the Response to Heat Stress

Daquinag, Alexes C.; Fadri, Maria; Jung, Sung Yun; Qin, Jun; Kunz, Jeannette

doi:10.1128/mcb.00461-06

Cited by 76 publications

(92 citation statements)

References 63 publications

(106 reference statements)

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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%

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

confidence: 52%

Section: Introductionmentioning

confidence: 99%

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

Guillas

Vernay

Vitagliano

et al. 2013

Journal of Cell Science

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“…Proteins in boldface type were analyzed in this study. Daquinag et al 2007). It was further shown that mutations in cnb1, encoding the regulatory subunit of calcineurin, suppress an avo3 temperature-sensitive mutation (Aronova et al 2008).…”

Section: Discussionmentioning

confidence: 99%

TORC2 Signaling Is Antagonized by Protein Phosphatase 2A and the Far Complex in Saccharomyces cerevisiae

Pracheil

Thornton²,

Liu

2012

Genetics

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The target of rapamycin (TOR) kinase, a central regulator of eukaryotic cell growth, exists in two essential, yet distinct, TOR kinase complexes in the budding yeast Saccharomyces cerevisiae: rapamycin-sensitive TORC1 and rapamycin-insensitive TORC2. Lst8, a component of both TOR complexes, is essential for cell viability. However, it is unclear whether the essential function of Lst8 is linked to TORC1, TORC2, or both. To that end, we carried out a genetic screen to isolate lst8 deletion suppressor mutants. Here we report that mutations in SAC7 and FAR11 suppress lethality of lst8D and TORC2-deficient (tor2-21) mutations but not TORC1 inactivation, suggesting that the essential function of Lst8 is linked only to TORC2. More importantly, characterization of lst8D bypass mutants reveals a role for protein phosphatase 2A (PP2A) in the regulation of TORC2 signaling. We show that Far11, a member of the Far3-7-8-9-10-11 complex involved in pheromone-induced cell cycle arrest, interacts with Tpd3 and Pph21, conserved components of PP2A, and deletions of components of the Far3-7-8-9-10-11 complex and PP2A rescue growth defects in lst8D and tor2-21 mutants. In addition, loss of the regulatory B9 subunit of PP2A Rts1 or Far11 restores phosphorylation to the TORC2 substrate Slm1 in a tor2-21 mutant. Mammalian Far11 orthologs FAM40A/B exist in a complex with PP2A known as STRIPAK, suggesting a conserved functional association of PP2A and Far11. Antagonism of TORC2 signaling by PP2A-Far11 represents a novel regulatory mechanism for controlling spatial cell growth of yeast.T HE target of rapamycin (TOR) kinase is a phosphatidylinositol kinase-related protein kinase that controls eukaryotic cell growth and proliferation in response to nutrient conditions (Inoki et al. 2005;Wullschleger et al. 2006;Zoncu et al. 2011). The TOR kinase is inhibited by the complex of rapamycin and Fpr1, a peptidyl-prolyl cis-trans isomerase. The TOR kinase is conserved in eukaryotes. Unlike fungal species, which may possess two TOR kinases, higher eukaryotes such as humans possess only one. The TOR kinase exists in multi-protein complexes, which have been purified from many different eukaryotic systems. There exist two distinct TOR kinase complexes. In yeast, rapamycin-sensitive TORC1 consists of Tor1 or Tor2, Lst8, Kog1, and Tco89, and rapamycin-insensitive TORC2 consists of Tor2, Lst8, Avo1, Avo2, Avo3, and Bit61 (Loewith et al. 2002;Wedaman et al. 2003;Reinke et al. 2004). Both complexes are partially conserved in mammals: mTORC1 contains the yeast Kog1 ortholog raptor, while mTORC2 contains mSin1 and rictor, orthologs of yeast Avo1 and Avo3, respectively; GbL, the ortholog of yeast Lst8, exists in both mTORC1 and mTORC2 (Zoncu et al. 2011).TOR regulates cell growth by sensing and responding to changes in nutrient conditions (Schmelzle and Hall 2000). TORC1 has an essential function involving the regulation of cell growth that is carried out when either Tor1 or Tor2 is in the complex. Under favorable growth conditions, TORC1 promotes ce...

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“…This void in our knowledge is beginning to be filled with the realization that these two pathways, along with the calcineurin signaling pathway, modulate the phosphorylation/dephosphorylation cycle of the Slm1 and Slm2 proteins during heat stress to control actin polarization, endocytosis, and sphingolipid metabolism (82)(83)(84).…”

Section: Cellular Processes Regulated By Lcbsmentioning

confidence: 99%

“…Heat stress was recently shown to initiate the dephosphorylation and rephosphorylation of the Slm proteins (83)(84)(85). Dephosphorylation was shown to be mediated by the protein phosphatase calcineurin, which binds to the Slm proteins (82-84) and plays roles in a variety of stress responses.…”

Section: Cellular Processes Regulated By Lcbsmentioning

confidence: 99%

Thematic Review Series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast

Dickson

2008

Journal of Lipid Research

206

215

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Our understanding of sphingolipid metabolism and functions in the baker's yeast Saccharomyces cerevisiae has progressed substantially in the past 2 years. Yeast sphingolipids contain a C 26 -acyl moiety, all of the genes necessary to make these long-chain fatty acids have been identified, and a mechanism for how chain length is determined has been proposed. Advances in understanding how the de novo synthesis of ceramide and complex sphingolipids is regulated have been made, and they demonstrate that the Target Of Rapamycin Complex 2 (TORC2) controls ceramide synthase activity. Other work shows that TORC2 regulates the level of complex sphingolipids in a pathway using the Slm1 and Slm2 proteins to control the protein phosphatase calcineurin, which regulates the breakdown of complex sphingolipids. The activity of Slm1 and Slm2 has also been shown to be regulated during heat stress by phosphoinositides and TORC2, along with sphingoid long-chain bases and the Pkh1 and Pkh2 protein kinases, to control the actin cytoskeleton, the trafficking of nutrient transporters, and cell viability.Together, these results provide the first molecular insights into understanding previous genetic interaction data that indicated a connection between sphingolipids and the TORC2 and phosphoinositide signaling networks. This new knowledge provides a foundation for greatly advancing our understanding of sphingolipid biology in yeast.-Dickson, R. C. New insights into sphingolipid metabolism and function in budding yeast. J. Lipid Res. 2008. 49: 909-921.

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The Yeast PH Domain Proteins Slm1 and Slm2 Are Targets of Sphingolipid Signaling during the Response to Heat Stress

Cited by 76 publications

References 63 publications

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

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

TORC2 Signaling Is Antagonized by Protein Phosphatase 2A and the Far Complex in Saccharomyces cerevisiae

Thematic Review Series: Sphingolipids. New insights into sphingolipid metabolism and function in budding yeast

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