Abstract
Drosophila Ceramide Synthase (CerS) Schlank regulates both ceramide synthesis and fat metabolism. Schlank contains a catalytic lag1p motif and, like many CerS in other species, a homeodomain of unknown function. Here, we show that the Drosophila CerS Schlank is imported into the nucleus and requires two nuclear localization signals (NLSs) within its homeodomain and functional Importin-β import machinery. Expression of Schlank variants containing the homeodomain without functional lag1p motif rescued the fat metabolism phenotype of schlank mutants whereas a variant with a mutated NLS site did not rescue. Thus, the homeodomain of Schlank is involved in the regulation of lipid metabolism independent of the catalytic lag1p motif.
Keywords:
Drosophila; ceramide synthase; homeodomain; importin; lipid homeostasis; nuclear function.
© 2016 Federation of European Biochemical Societies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Active Transport, Cell Nucleus
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Amino Acid Motifs
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Amino Acid Substitution
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Animals
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Animals, Genetically Modified
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Catalytic Domain
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Cell Line
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Cell Nucleus / enzymology
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Cell Nucleus / metabolism*
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Drosophila Proteins / antagonists & inhibitors
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Drosophila Proteins / chemistry
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / cytology
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Fat Body / cytology
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Fat Body / enzymology
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Fat Body / metabolism*
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Green Fluorescent Proteins / genetics
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Green Fluorescent Proteins / metabolism
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Homeodomain Proteins / chemistry
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Lipid Metabolism*
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Mutation
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Nuclear Localization Signals / chemistry
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Nuclear Localization Signals / genetics
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Nuclear Localization Signals / metabolism*
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / chemistry
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Interaction Domains and Motifs
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RNA Interference
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / metabolism
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Sphingosine N-Acyltransferase / antagonists & inhibitors
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Sphingosine N-Acyltransferase / chemistry
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Sphingosine N-Acyltransferase / genetics
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Sphingosine N-Acyltransferase / metabolism*
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beta Karyopherins / antagonists & inhibitors
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beta Karyopherins / genetics
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beta Karyopherins / metabolism
Substances
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Drosophila Proteins
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Fs(2)Ket protein, Drosophila
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Homeodomain Proteins
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Nuclear Localization Signals
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Peptide Fragments
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Recombinant Fusion Proteins
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beta Karyopherins
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Green Fluorescent Proteins
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Schlank protein, Drosophila
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Sphingosine N-Acyltransferase