High impact information on LAG1

• In this study, we expressed tagged versions of Lac1p and Lag1p and purified them to near homogeneity [1].
• C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p [2].
• In Caenorhabditis elegans, the GLP-1 receptor acts with a downstream transcriptional regulator, LAG-1, to mediate intercellular signaling [3].
• Because both sphingolipid synthesis and LAG1 facilitate endocytosis of glycosylphosphatidylinositol-anchored proteins in yeast, we propose a role for Asc-1 in a salvage mechanism of sphingolipid-depleted plant cells [4].
• Transfection with the yeast gene Lag1 Sc and the human homolog LASS1 increased ceramide levels and partially corrected growth and apoptosis in CLN9-deficient cells [5].

Biological context of LAG1

• Homologues of Lag1p have been identified in higher eukaryotes, including human, raising the possibility that ceramide and other sphingolipid metabolites play a wider role in biological aging [6].
• We have identified two genes in Saccharomyces cerevisiae, LAG1 and a novel gene termed DGT1 (for "delayed GPI-anchored protein transport"), encoding structurally related proteins with multiple membrane-spanning domains [7].
• Deletion of either gene caused no detectable phenotype, whereas lag1Delta dgt1Delta cells displayed growth defects and a significant delay in ER-to-Golgi transport of GPI-anchored proteins, suggesting that LAG1 and DGT1 encode functionally redundant or overlapping proteins [7].
• LAG1 contributes to the substrate specificity and catalytic activity of ceramide synthases in Saccharomyces cerevisiae [8].
• The N- and C-termini of the proteins are in the cytoplasm and eight putative membrane-spanning domains were identified in Lag1p and Lac1p by insertion of glycosylation and factor Xa cleavage sites at various positions [9].

Anatomical context of LAG1

• Lag1p and Lac1p are two homologous transmembrane proteins of the endoplasmic reticulum in Saccharomyces cerevisiae [10].
• In this study, we show that lag1 Delta lac1 Delta cells have reduced sphingolipid levels due to a block of the fumonisin B1-sensitive and acyl-CoA-dependent ceramide synthase reaction [10].
• Consistent with a role of Lag1p and Dgt1p in GPI-anchored protein transport, lag1Delta dgt1Delta cells deposit abnormal, multilayered cell walls [7].

Associations of LAG1 with chemical compounds

• Based on these data, LAG1 and LAC1 are the first genes to be identified that are required for the fumonisin B1-sensitive and acyl-CoA-dependent ceramide synthase reaction [10].
• Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae [10].
• Moreover, lag1 Delta lac1 Delta cells are resistant to aureobasidin A, an inhibitor of the inositolphosphorylceramide synthase, suggesting that aureobasidin A may be toxic because it leads to increased ceramide levels [10].
• We also present evidence that histidine and aspartic acid residues in the Lag motif are essential for the function of Lag1p in vivo [9].

Other interactions of LAG1

• Although a hyperactive Pdr pathway altered the profile of sphingolipids produced, the loss of either LAC1 or LAG1 alone failed to produce further changes [11].
• Studies with the UTH genes have implicated changes in transcriptional silencing during yeast ageing, but the roles of the RAS2, LAG1 and PHB1 genes in regulating yeast longevity are still unclear [12].
• Controlled by either the natural weak LAG1 promoter or the strong yeast ADH1 promoter, LASS2 and LASS2DeltaHOX could not rescue the slow growth defect of double mutant [8].
• Instead, we propose that Lag1p and Dgt1p facilitate efficient ER-to-Golgi transport of GPI-anchored proteins [7].

Analytical, diagnostic and therapeutic context of LAG1

• Reporter gene, Northern blot, and Western blot assays indicated that the expression level of Lac1p is approximately three times that of Lag1p [11].

References