Targeting of the <i>Drosophila</i> protein CG2254/Ldsdh1 to a subset of lipid droplets

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  • Peter J. Thul
    Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf 1 , Düsseldorf 40225 , Germany
  • Kirsten Tschapalda
    Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf 1 , Düsseldorf 40225 , Germany
  • Petra Kolkhof
    Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf 1 , Düsseldorf 40225 , Germany
  • Abdou Rachid Thiam
    Ecole Normale Superieure, PSL Research University, Universite de Paris Diderot Sorbonne Paris-Cite 5 Laboratoire de Physique Statistique , , Paris 75005 , France
  • Monika Oberer
    Institute of Molecular Biosciences, BioTechMed Graz, University of Graz 6 , Graz 8010   Austria
  • Mathias Beller
    Institute for Mathematical Modeling of Biological Systems, Heinrich Heine University Düsseldorf 1 , Düsseldorf 40225 , Germany

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<jats:title>ABSTRACT</jats:title> <jats:p>Lipid droplets (LDs) are the principal organelles of lipid storage. They consist of a hydrophobic core of storage lipids, surrounded by a phospholipid monolayer with proteins attached. While some of these proteins are known to be essential for the regulation of cellular and organismic lipid metabolism, key questions concerning LD protein function, such as their targeting to LDs, are still unanswered. Intriguingly, some proteins are restricted to subsets of LDs by an as-yet-unknown mechanism. This finding makes LD targeting even more complex. Here, we characterize the Drosophila protein CG2254, which is targeted to subsets of LDs in cultured cells and in different larval Drosophila tissues, where the prevalence of subsets of LDs appears highly dynamic. We find that an amphipathic amino acid stretch mediates CG2254 LD localization. Additionally, we identified a juxtaposed sequence stretch limiting CG2254 localization to a subset of LDs. This sequence is sufficient to restrict a chimeric protein consisting of the subset-targeting sequence introduced to an otherwise pan-LD-localized protein sequence to a subset of LDs. Based on its subcellular localization and annotated function, we suggest that CG2254 is renamed Lipid droplet subset dehydrogenase 1 (Ldsdh1).</jats:p>

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