Brave little yeast, please guide us to Thebes: sphingolipid function in S. cerevisiae

Schneiter, Roger

doi:10.1002/(sici)1521-1878(199912)22:1<1004::aid-bies4>3.0.co;2-y

Cited by 57 publications

(21 citation statements)

References 71 publications

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“…In addition to glycerophospholipids, yeast cells contain a second class of phospholipids termed sphingolipids (Schneiter 1999;Guan and Wenk 2006;Dickson 2010). These lipids are derived from sphingosine or phytosphingosine, which are produced in a condensation reaction between serine and palmitoyl-CoA.…”

Section: Sphingolipidsmentioning

confidence: 99%

Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor

Kohlwein

2017

Cold Spring Harb Protoc

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Lipids are essential biomolecules with diverse biological functions, ranging from building blocks for all biological membranes to energy substrates, signaling molecules, and protein modifiers. Despite advances in lipid analytics by mass spectrometry, the extraction and quantitative analysis of the diverse classes of lipids are still an experimental challenge. Yeast is a model organism that provides several advantages for studying lipid metabolism, because most biosynthetic pathways are well described and a great deal of information is available on the regulatory mechanisms that control lipid homeostasis. In addition, the composition of yeast lipids is much less complex than that of mammalian lipids, making yeast an excellent reference system for studying lipid-associated cell functions.

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Section: Sphingolipidsmentioning

confidence: 99%

Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor

Kohlwein

2017

Cold Spring Harb Protoc

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“…From the ER, ceramide is transported both by vesicular and non-vesicular routes to the Golgi apparatus, where it is converted to sphingolipids [22,23]. Mature sphingolipids are then transported to the plasma membrane, where they are highly enriched [24,25] (Fig. 1).…”

Section: Coupling Of H D -Atpase Biogenesis To Sphingolipid Synthesismentioning

confidence: 99%

Lipid-dependent surface transport of the proton pumping ATPase: A model to study plasma membrane biogenesis in yeast

Toulmay

Schneiter

2007

Biochimie

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The proton pumping H þ -ATPase, Pma1, is one of the most abundant integral membrane proteins of the yeast plasma membrane. Pma1 activity controls the intracellular pH and maintains the electrochemical gradient across the plasma membrane, two essential cellular functions. The maintenance of the proton gradient, on the other hand, also requires a specialized lipid composition of this membrane. The plasma membrane of eukaryotic cells is typically rich in sphingolipids and sterols. These two lipids condense to form less fluid membrane microdomains or lipid rafts. The yeast sphingolipid is peculiar in that it invariably contains a saturated very long-chain fatty acid with 26 carbon atoms. During cell growth and plasma membrane expansion, both C26-containing sphingolipids and Pma1 are first synthesized in the endoplasmatic reticulum from where they are transported by the secretory pathway to the cell surface. Remarkably, shortening the C26 fatty acid to a C22 fatty acid by mutations in the fatty acid elongation complex impairs raft association of newly synthesized Pma1 and induces rapid degradation of the ATPase by rerouting the enzyme from the plasma membrane to the vacuole, the fungal equivalent of the lysosome. Here, we review the role of lipids in mediating raft association and stable surface transport of the newly synthesized ATPase, and discuss a model, in which the newly synthesized ATPase assembles into a membrane environment that is enriched in C26-containing lipids already in the endoplasmatic reticulum. The resulting proteinelipid complex is then transported and sorted as an entity to the plasma membrane. Failure to successfully assemble this lipideprotein complex results in mistargeting of the protein to the vacuole.

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“…Sphingolipids are ceramide-containing lipids that are highly enriched in the outer leaflet of the plasma membrane, where they exert both structural and signaling functions (for review see Dickson, 1998;Schneiter, 1999). In fungi, these lipids are composed of an inositolphosphate-containing hydrophilic head group bound to phytoceramide.…”

Section: Introductionmentioning

confidence: 99%

A Specific Structural Requirement for Ergosterol in Long-chain Fatty Acid Synthesis Mutants Important for Maintaining Raft Domains in Yeast

Eisenkolb

Zenzmaier

Leitner

et al. 2002

MBoC

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115

120

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Fungal sphingolipids contain ceramide with a very-long-chain fatty acid (C26). To investigate the physiological significance of the C26-substitution on this lipid, we performed a screen for mutants that are synthetically lethal with ELO3. Elo3p is a component of the ER-associated fatty acid elongase and is required for the final elongation cycle to produce C26 from C22/C24 fatty acids. elo3⌬ mutant cells thus contain C22/C24-instead of the natural C26-substituted ceramide. We now report that under these conditions, an otherwise nonessential, but also fungal-specific, structural modification of the major sterol of yeast, ergosterol, becomes essential, because mutations in ELO3 are synthetically lethal with mutations in ERG6. Erg6p catalyzes the methylation of carbon atom 24 in the aliphatic side chain of sterol. The lethality of an elo3⌬ erg6⌬ double mutant is rescued by supplementation with ergosterol but not with cholesterol, indicating a vital structural requirement for the ergosterol-specific methyl group. To characterize this structural requirement in more detail, we generated a strain that is temperature sensitive for the function of Erg6p in an elo3⌬ mutant background. Examination of raft association of the GPI-anchored Gas1p and plasma membrane ATPase, Pma1p, in the conditional elo3⌬ erg6 ts double mutant, revealed a specific defect of the mutant to maintain raft association of preexisting Pma1p. Interestingly, in an elo3⌬ mutant at 37°C, newly synthesized Pma1p failed to enter raft domains early in the biosynthetic pathway, and upon arrival at the plasma membrane was rerouted to the vacuole for degradation. These observations indicate that the C26 fatty acid substitution on lipids is important for establishing raft association of Pma1p and stabilizing the protein at the cell surface. Analysis of raft lipids in the conditional mutant strain revealed a selective enrichment of ergosterol in detergent-resistant membrane domains, indicating that specific structural determinants on both sterols and sphingolipids are required for their association into raft domains.

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Brave little yeast, please guide us to Thebes: sphingolipid function in S. cerevisiae

Cited by 57 publications

References 71 publications

Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor

Analyzing and Understanding Lipids of Yeast: A Challenging Endeavor

Lipid-dependent surface transport of the proton pumping ATPase: A model to study plasma membrane biogenesis in yeast

A Specific Structural Requirement for Ergosterol in Long-chain Fatty Acid Synthesis Mutants Important for Maintaining Raft Domains in Yeast

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