The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Necessary Role for the Lag1p Motif in (Dihydro)ceramide Synthase Activity
Open accessAbstract
Lag1 (longevity assurance gene 1) homologues, a family of transmembrane proteins found in all eukaryotes, have been shown to be necessary for (dihydro)ceramide synthesis. All Lag1 homologues contain a highly conserved stretch of 52 amino acids known as the Lag1p motif. However, the functional significance of the conserved Lag1p motif for (dihydro)ceramide synthesis is currently unknown. In this work, we have investigated the function of the motif by introducing eight point mutations in the Lag1p motif of the mouse LASS1 (longevity assurance homologue 1 of yeast Lag1). The (dihydro)ceramide synthase activity of the mutants was tested using microsomes in HeLa cells and in vitro. Six of the mutations resulted in loss of activity in cells and in vitro. In addition, our results showed that C18:0 fatty acid CoA (but not cis-C18:1 fatty acid CoAs) are substrates for LASS1 and that LASS1 in HeLa cells is sensitive to fumonisin B1, an in vitro inhibitor of (dihydro)ceramide synthase. Moreover, we mutated the Lag1p motif of another Lag homologue, human LASS5. The amino acid substitutions in the human LASS5 were the same as in mouse LASS1, and had the same effect on the in vitro activity of LASS5, suggesting the Lag1p motif appears to be essential for the enzyme activity of all Lag1 homologues.
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“Transmembrane spanning Ceramide synthase (CERS1) is a key enzyme in sphingolipid metabolism which uses acyl-CoA to generate ceramides with various acyl chain lengths that regulate differentiation, proliferation, and apoptosis (27).”
From Accurate prediction of protein structures and interactions using a 3-track network (2021) · cites this paper as [27]
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Metadata
- Authors
- Spassieva, S., Seo, J.-G., Jiang, J. C., Bielawski, J., Alvarez-Vasquez, F., Jazwinski, S. M., Hannun, Y. A., & Obeid, L. M.
- Affiliations
- Medical University of South Carolina (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- Corresponding author
- Obeid, Lina M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 281
- Issue
- 45
- Pages
- 33931-33938
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2062250309
- Cited by
- 121
- References
- 31
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 9 · 2022: 3 · 2021: 7 · 2020: 3 · 2019: 4 · 2018: 9 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 9 · 2012: 13
- FWCI
- 2.85
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-016583, R01AG016583, AG 006168)
- National Cancer Institute (P01CA97132, P01CA097132)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Health Sciences › Medicine › Genetics (clinical) › Lysosomal Storage Disorders Research
- Keywords
- ceramide synthesis, transmembrane proteins, point mutations, fumonisin B1, enzyme activity, HeLa cells
- MeSH terms
- Amino Acid Sequence, Animals, Ceramides, HeLa Cells, Humans, Membrane Proteins, Microsomes, Molecular Sequence Data, Oxidoreductases, Phosphates, Transfection, Blotting, Western, Mutagenesis, Site-Directed, Point Mutation, Sequence Homology, Amino Acid, Protein Structure, Tertiary, Amino Acid Substitution, Spectrometry, Mass, Electrospray Ionization, Sphingosine N-Acyltransferase, Mice
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