Nuclear Drosophila CerS Schlank regulates lipid homeostasis via the homeodomain, independent of the lag1p motif

André Voelzmann, Anna-Lena Wulf, Franka Eckardt, Melanie Thielisch, Mirco Brondolin, Yanina-Yasmin Pesch, Mariangela Sociale, Reinhard Bauer, Michael Hoch

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)971-81
Number of pages11
JournalFEBS Letters
Volume590
Issue number7
DOIs
Publication statusPublished - Apr 2016

Keywords

  • Active Transport, Cell Nucleus
  • Amino Acid Motifs
  • Amino Acid Substitution
  • Animals
  • Animals, Genetically Modified
  • Catalytic Domain
  • Cell Line
  • Cell Nucleus
  • Drosophila Proteins
  • Drosophila melanogaster
  • Fat Body
  • Green Fluorescent Proteins
  • Homeodomain Proteins
  • Lipid Metabolism
  • Mutation
  • Nuclear Localization Signals
  • Peptide Fragments
  • Protein Interaction Domains and Motifs
  • RNA Interference
  • Recombinant Fusion Proteins
  • Sphingosine N-Acyltransferase
  • beta Karyopherins
  • Journal Article
  • Research Support, Non-U.S. Gov't

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