title: Nuclear Drosophila CerS Schlank regulates lipid homeostasis via the homeodomain, independent of the lag1p motif.
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.
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: André
authors.identifier: http://orcid.org/0000-0002-7682-5637
authors.initials: A
authors.lastname: Voelzmann
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Wulf
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Franka
authors.initials: F
authors.lastname: Eckardt
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Thielisch
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Mirco
authors.identifier: http://orcid.org/0000-0002-3787-6183
authors.initials: M
authors.lastname: Brondolin
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Yanina-Yasmin
authors.initials: YY
authors.lastname: Pesch
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Sociale
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Bauer
authors.affiliation: Program Unit Development, Genetics & Molecular Physiology, Laboratory for Molecular Developmental Biology, LIMES-Institute, University of Bonn, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hoch
mesh_terms: D021581:Active Transport, Cell Nucleus; D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D030801:Animals, Genetically Modified; D020134:Catalytic Domain; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D005216:Fat Body / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050356:Lipid Metabolism; D009154:Mutation; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D051049:Sphingosine N-Acyltransferase / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D028961:beta Karyopherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C424162:Fs(2)Ket protein, Drosophila; D018398:Homeodomain Proteins; D019913:Nuclear Localization Signals; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D028961:beta Karyopherins; D049452:Green Fluorescent Proteins; C555760:Schlank protein, Drosophila; D051049:Sphingosine N-Acyltransferase
keywords: Drosophila; ceramide synthase; homeodomain; importin; lipid homeostasis; nuclear function