High impact information on SUR4

• By complementing the homologous yeast mutants, we found that Ssc1 could rescue normal sphingolipid synthesis in the sur4/elo3 mutant lacking the ability to synthesize cerotic acid (C(26:0)) [1].
• Recessive mutations in either VBM1 or VBM2, which encode related ER-localized membrane proteins, allow yeast to grow normally and secrete in the absence of Snc v-SNAREs [2].
• These phenotypes are exacerbated by the deletion of either the ELO2 or ELO3 gene, both of which have previously been shown to be required for VLCFA synthesis [3].
• There are three ELO genes in yeast that encode the homologous Elo1p, Elo2p, and Elo3p proteins [4].
• 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 [5].

Biological context of SUR4

• Elo3p apparently has a broader substrate specificity and is essential for the conversion of 24-carbon acids to 26-carbon species [6].
• 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 [6].
• In an expression study on tridemorph-containing medium, using the inducible GAL1 promoter fused to the ELO3 open reading frame, we demonstrated that suppression occurred only when ELO3 was not expressed [7].

Anatomical context of SUR4

• These data and other aspects implicating SUR4 in glucose metabolism, suggest an involvement of these genes in the dynamics of cortical actin cytoskeleton in response to nutrient availability [8].

Associations of SUR4 with chemical compounds

• Strains with deletions of SYR3/ELO2 and ELO3 were resistant to syringomycin E, and lipid analyses of both mutants revealed shortened fatty acid chains and lower levels of sphingolipids [9].
• The Elo3 protein is necessary for synthesis of C(26)-CoA, which in wild-type yeast is a source of C(26) fatty acyls found in the ceramide moieties of all sphingolipids [10].
• In addition, both the elo3 and cka2 mutants showed increased sensitivity to the CS inhibitors australifungin and fumonisin B(1) [10].
• Disruption of the sterol isomerase-encoding gene is lethal in cells growing in the absence of exogenous ergosterol, except in SR-resistant mutants lacking either the SUR4 or the FEN1 gene product [11].
• The results suggest that sterol isomerase is the target of SR 31747 and that both the SUR4 and FEN1 gene products are required to mediate the proliferation arrest induced by ergosterol depletion [11].

Other interactions of SUR4

• Green fluorescent protein-tagged Ybr159p co-localizes and co-immunoprecipitates with other elongating enzymes, Elo3p and Tsc13p [12].
• These suppressor genes (designated SRE1 and SRE2) are distinct from RAD3 and do not suppress the phenotype of several other temperature-sensitive mutants tested [13].

Analytical, diagnostic and therapeutic context of SUR4

• 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 [6].

References