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Gene Review

LAG1  -  sphingosine N-acyltransferase LAG1

Saccharomyces cerevisiae S288c

Synonyms: Longevity assurance factor 1, Longevity assurance gene 1 protein, Longevity assurance protein 1, Sphingosine N-acyltransferase LAG1, YHL003C
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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


Associations of LAG1 with chemical compounds


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


  1. Lip1p: a novel subunit of acyl-CoA ceramide synthase. Vallée, B., Riezman, H. EMBO J. (2005) [Pubmed]
  2. C26-CoA-dependent ceramide synthesis of Saccharomyces cerevisiae is operated by Lag1p and Lac1p. Guillas, I., Kirchman, P.A., Chuard, R., Pfefferli, M., Jiang, J.C., Jazwinski, S.M., Conzelmann, A. EMBO J. (2001) [Pubmed]
  3. Roles of the RAM and ANK domains in signaling by the C. elegans GLP-1 receptor. Roehl, H., Bosenberg, M., Blelloch, R., Kimble, J. EMBO J. (1996) [Pubmed]
  4. A longevity assurance gene homolog of tomato mediates resistance to Alternaria alternata f. sp. lycopersici toxins and fumonisin B1. Brandwagt, B.F., Mesbah, L.A., Takken, F.L., Laurent, P.L., Kneppers, T.J., Hille, J., Nijkamp, H.J. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. The CLN9 protein, a regulator of dihydroceramide synthase. Schulz, A., Mousallem, T., Venkataramani, M., Persaud-Sawin, D.A., Zucker, A., Luberto, C., Bielawska, A., Bielawski, J., Holthuis, J.C., Jazwinski, S.M., Kozhaya, L., Dbaibo, G.S., Boustany, R.M. J. Biol. Chem. (2006) [Pubmed]
  6. Suppressor analysis points to the subtle role of the LAG1 ceramide synthase gene in determining yeast longevity. Jiang, J.C., Kirchman, P.A., Allen, M., Jazwinski, S.M. Exp. Gerontol. (2004) [Pubmed]
  7. Two endoplasmic reticulum (ER) membrane proteins that facilitate ER-to-Golgi transport of glycosylphosphatidylinositol-anchored proteins. Barz, W.P., Walter, P. Mol. Biol. Cell (1999) [Pubmed]
  8. Expression of LASS2 controlled by LAG1 or ADH1 promoters cannot functionally complement Lag1p. Yu, Y., Lu, H., Pan, H., Ma, J.H., Ding, Z.J., Li, Y.Y. Microbiol. Res. (2006) [Pubmed]
  9. Transmembrane topology of ceramide synthase in yeast. Kageyama-Yahara, N., Riezman, H. Biochem. J. (2006) [Pubmed]
  10. Lag1p and Lac1p are essential for the Acyl-CoA-dependent ceramide synthase reaction in Saccharomyces cerevisae. Schorling, S., Vallée, B., Barz, W.P., Riezman, H., Oesterhelt, D. Mol. Biol. Cell (2001) [Pubmed]
  11. Differential regulation of ceramide synthase components LAC1 and LAG1 in Saccharomyces cerevisiae. Kolaczkowski, M., Kolaczkowska, A., Gaigg, B., Schneiter, R., Moye-Rowley, W.S. Eukaryotic Cell (2004) [Pubmed]
  12. Review: to bud until death: the genetics of ageing in the yeast, Saccharomyces. Austriaco, N.R. Yeast (1996) [Pubmed]
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