Characterization of a new gene family developing pleiotropic phenotypes upon mutation inSaccharomyces cerevisiae

Revardel, Emmanuelle; Bonneau, M.; Durrens, Pascal; Aigle, Michel

doi:10.1016/0167-4781(95)00124-y

Cited by 61 publications

(56 citation statements)

References 25 publications

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“…Fen1 and Sur4 elongate long-chain acyl-CoAs to C22:0-CoA (weakly to C24:0-CoA) and C26:0-CoA, respectively (17,18). Because VLCFA production is essential for yeast growth, double deletion of FEN1 and SUR4 genes is lethal (19,20). Reportedly, ELOVL1 can rescue the lethality of Δfen1 Δsur4 cells (12).…”

Section: Resultsmentioning

confidence: 99%

ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

Ohno

Suto

Yamanaka

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

305

354

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Very long-chain fatty acids (VLCFAs) exert a variety of cellular functions and are associated with numerous diseases. However, the precise pathway behind their elongation has remained elusive. Moreover, few regulatory mechanisms for VLCFAs synthesis have been identified. Elongases catalyze the first of four steps in the VLCFA elongation cycle; mammals have seven elongases (ELO-VL1-7). In the present study, we determined the precise substrate specificities of all the ELOVLs by in vitro analyses. Particularly notable was the high activity exhibited by ELOVL1 toward saturated and monounsaturated C20-and C22-CoAs, and that it was essential for the production of C24 sphingolipids, which are unique in their capacity to interdigitate within the membrane as a result of their long chain length. We further established that ELOVL1 activity is regulated with the ceramide synthase CERS2, an enzyme essential for C24 sphingolipid synthesis. This regulation may ensure that the production of C24-CoA by elongation is coordinated with its utilization. Finally, knockdown of ELOVL1 caused a reduction in the activity of the Src kinase LYN, confirming that C24-sphingolipids are particularly important in membrane microdomain function.acyl-CoA | lipid metabolism | monounsaturated fatty acid | polyunsaturated fatty acid | saturated fatty acid

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Section: Resultsmentioning

confidence: 99%

ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

Ohno

Suto

Yamanaka

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

305

354

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“…Mutations or disruptions of ELO2 and ELO3 were previously reported as affecting ␤-glucan synthase activity (12), the plasma membrane, (H ϩ )-ATPase (14), bud localization defects (13), and resistance to sterol synthesis inhibitors (11,13). All of these functions are apparently produced by the activities of intrinsic membrane proteins, which could be affected by changes in the composition of their lipid environment or by the absence of an essential sphingolipid-membrane protein interaction.…”

Section: Elo2 and Elo3 Function In Fatty Acid Elongationmentioning

confidence: 99%

“…Those mutants confer resistance to echinocandins and have defects in ␤-glucan synthase activities. It was also reported as FEN1 (11,13), a gene whose mutants exhibited bud localization defects and resistance to the sterol isomerase inhibitor SR 31747. ELO3 was previously cloned and identified, respectively, as APA1 with mutant alleles that cause a decrease in the level of the plasma membrane ATPase (14), SUR4 (15), whose mutants suppress the reduced viability on starvation mutant phenotype (rvs161), and SRE1 (11) whose mutants suppress the effects of the steroid isomerase inhibitor, SR 31747.…”

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confidence: 99%

“…ELO3 was previously cloned and identified, respectively, as APA1 with mutant alleles that cause a decrease in the level of the plasma membrane ATPase (14), SUR4 (15), whose mutants suppress the reduced viability on starvation mutant phenotype (rvs161), and SRE1 (11) whose mutants suppress the effects of the steroid isomerase inhibitor, SR 31747. At least two laboratories have reported that simultaneous disruption of ELO2 and ELO3 produces a lethal phenotype (11,13) which indicates that their encoded proteins have related and overlapping functions. Similar studies in this laboratory also support the synthetic lethality of the double disruptions.…”

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confidence: 99%

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ELO2 and ELO3, Homologues of theSaccharomyces cerevisiae ELO1 Gene, Function in Fatty Acid Elongation and Are Required for Sphingolipid Formation

Oh¹,

Toke²,

Mandala³

et al. 1997

Journal of Biological Chemistry

449

507

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ELO2 and ELO3 were identified from the Saccharomyces cerevisiae genome data base as homologues of ELO1, a gene involved in the elongation of the fatty acid 14:0 to 16:0. Mutations in these genes have previously been shown to produce pleiotropic effects involving a number of membrane functions. The simultaneous disruption of ELO2 and ELO3 has also been shown to produce synthetic lethality, indicating that they have related and/or overlapping functions. Gas chromatography and gas chromatography/mass spectroscopy analyses reveal that null mutations of ELO2 and ELO3 produce defects in the formation of very long chain fatty acids. Analysis of the null mutants indicates that these genes encode components of the membrane-bound fatty acid elongation systems that produce the 26-carbon very long chain fatty acids that are precursors for ceramide and sphingolipids. Elo2p appears to be involved in the elongation of fatty acids up to 24 carbons. It appears to have the highest affinity for substrates with chain lengths less than 22 carbons. Elo3p apparently has a broader substrate specificity and is essential for the conversion of 24-carbon acids to 26-carbon species. Disruption of either gene reduces cellular sphingolipid levels and results in the accumulation of the long chain base, phytosphingosine. Null mutations in ELO3 result in accumulation of labeled precursors into inositol phosphoceramide, with little labeling in the more complex mannosylated sphingolipids, whereas disruption of ELO2 results in reduced levels of all sphingolipids.In the yeast Saccharomyces cerevisiae, sphingolipids comprise approximately 10% of the total membrane lipid species (1). The hydrophobic moiety of these lipids is ceramide, which consists of a long chain base coupled to a very long chain fatty acid that is almost exclusively 26:0 1 or hydroxy 26:0 (2). Although sphingolipids are relatively minor membrane lipid species, they are highly concentrated on the plasma membrane and appear to be essential for a number of critical membrane and cellular functions (3-5). Inhibition of sphingolipid biosynthesis results in growth inhibition and cell death (6, 7). Ceramide has also been implicated as a component of an essential cell signaling pathways in Saccharomyces (8).In wild type cells, most fatty acids are 12-18-carbon species that are found in glycerolipids. Those species appear to be formed de novo by the well characterized soluble cytoplasmic fatty acid synthase complex. The very long chain (20ϩ carbon) fatty acids found in sphingolipids, however, are formed by membrane-bound fatty acid elongation systems that are not well characterized. These enzyme systems extend 14 -18-carbon fatty acids by 2-carbon units by a sequence of reactions similar to those catalyzed by fatty acid synthases, with the exception of one reduction step, which in mammalian cells appears to be mediated by cytochrome b 5 (9).We recently identified a gene (ELO1) that encodes a membrane protein involved in the elongation of 14:0 to 16:0 (10). Comparison of the amino acid sequen...

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“…Counts were done in 10 cells for each strain and each growth condition; (-) means no cell in the corresponding class. Revardel et al, 1995). Recently, the sur4 or fen1 mutations were shown to suppress the snc1, snc2 mutations (David et al, 1998).…”

Section: Suppression Of Vesicle Accumulation By Sur4-vbm1 or Fen1-vbmmentioning

confidence: 99%

The yeast Rvs161 and Rvs167 proteins are involved in secretory vesicles targeting the plasma membrane and in cell integrity

Breton¹,

Schaeffer²,

Aigle³

2001

Yeast

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The Rvs161 and Rvs167 proteins are known to play a role in actin cytokeleton organization and endocytosis. Moreover, Rvs167p functionally interacts with the myosin Myo2p. Therefore, we explored the involvement of the Rvs proteins in vesicle traffic and in cell integrity. The rvs mutants accumulate late secretory vesicles at sites of membrane and cell wall construction. They are synthetic-lethal with the slt2/mpk1 mutation, which affects the MAP kinase cascade controlled by Pkc1p and is required for cell integrity. The phenotype of the double mutants is close to that described for the pkc1 mutant. Synthetic defects for growth are also observed with mutation in KRE6, a gene coding for a glucan synthase, required for cell wall construction. These data support the idea that the Rvs proteins are involved in the late targeting of vesicles whose cargoes are required for cell wall construction.

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Characterization of a new gene family developing pleiotropic phenotypes upon mutation inSaccharomyces cerevisiae

Cited by 61 publications

References 25 publications

ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

ELO2 and ELO3, Homologues of theSaccharomyces cerevisiae ELO1 Gene, Function in Fatty Acid Elongation and Are Required for Sphingolipid Formation

The yeast Rvs161 and Rvs167 proteins are involved in secretory vesicles targeting the plasma membrane and in cell integrity

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