title: The evolutionarily conserved protein CG9186 is associated with lipid droplets, required for their positioning and for fat storage.
abstract: Lipid droplets (LDs) are specialized cell organelles for the storage of energy-rich lipids. Although lipid storage is a conserved feature of all cells and organisms, little is known about fundamental aspects of the cell biology of LDs, including their biogenesis, structural assembly and subcellular positioning, and the regulation of organismic energy homeostasis. We identified a novel LD-associated protein family, represented by the Drosophila protein CG9186 and its murine homolog MGI:1916082. In the absence of LDs, both proteins localize at the endoplasmic reticulum (ER). Upon lipid storage induction, they translocate to LDs using an evolutionarily conserved targeting mechanism that acts through a 60-amino-acid targeting motif in the center of the CG9186 protein. Overexpression of CG9186, and MGI:1916082, causes clustering of LDs in both tissue culture and salivary gland cells, whereas RNAi knockdown of CG9186 results in a reduction of LDs. Organismal RNAi knockdown of CG9186 results in a reduction in lipid storage levels of the fly. The results indicate that we identified the first members of a novel and evolutionarily conserved family of lipid storage regulators, which are also required to properly position LDs within cells.
authors.affiliation: Department of Molecular Developmental Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Thiel
authors.forename: Christoph
authors.initials: C
authors.lastname: Heier
authors.forename: Verena
authors.initials: V
authors.lastname: Haberl
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Thul
authors.forename: Monika
authors.initials: M
authors.lastname: Oberer
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.forename: Herbert
authors.initials: H
authors.lastname: Jäckle
authors.forename: Mathias
authors.initials: M
authors.lastname: Beller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002265:Carboxylic Ester Hydrolases; D002478:Cells, Cultured; D017124:Conserved Sequence / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D019143:Evolution, Molecular; D006706:Homeostasis; D050356:Lipid Metabolism / Q000235:genetics; D008071:Lipoprotein Lipase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D021382:Protein Sorting Signals / Q000235:genetics; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D012469:Salivary Glands / Q000648:ultrastructure*; D019076:Transgenes / Q000235:genetics; D014617:Vacuoles / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D029721:Drosophila Proteins; C585048:MGI 1916082 protein, mouse; D021382:Protein Sorting Signals; D011506:Proteins; D034741:RNA, Small Interfering; D002265:Carboxylic Ester Hydrolases; C585047:sturkopf protein, Drosophila; D008071:Lipoprotein Lipase
keywords: Drosophila melanogaster; Lipid droplets; Lipid metabolism; Organelle clustering; Organelle positioning