The protein kinase CK2 substrate Jabba modulates lipid metabolism during Drosophila oogenesis

J Biol Chem. 2018 Feb 23;293(8):2990-3002. doi: 10.1074/jbc.M117.814657. Epub 2018 Jan 11.

Abstract

Lipid metabolism plays a critical role in female reproduction. During oogenesis, maturing oocytes accumulate high levels of neutral lipids that are essential for both energy production and the synthesis of other lipid molecules. Metabolic pathways within the ovary are partially regulated by protein kinases that link metabolic status to oocyte development. Although the functions of several kinases in this process are well established, the roles that many other kinases play in coordinating metabolic state with female germ cell development are unknown. Here, we demonstrate that the catalytic activity of casein kinase 2 (CK2) is essential for Drosophila oogenesis. Using an unbiased biochemical screen that leveraged an unusual catalytic property of the kinase, we identified a novel CK2 substrate in the Drosophila ovary, the lipid droplet-associated protein Jabba. We show that Jabba is essential for modulating ovarian lipid metabolism and for regulating female fertility in the fly. Our findings shed light on a CK2-dependent signaling pathway governing lipid metabolism in the ovary and provide insight into the long-recognized but poorly understood association between energy metabolism and female reproduction.

Keywords: CK2; Drosophila; Jabba; casein kinase 2; lipid droplet; lipid metabolism; oogenesis; protein kinase; reproduction; signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Animals, Genetically Modified
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Casein Kinase II / antagonists & inhibitors
  • Casein Kinase II / chemistry
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Crosses, Genetic
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Female
  • Gene Expression Regulation, Developmental*
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Humans
  • Lipid Metabolism*
  • Mice
  • Microscopy, Fluorescence
  • Oogenesis*
  • Ovary / cytology
  • Ovary / enzymology
  • Ovary / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / metabolism
  • Substrate Specificity

Substances

  • Carrier Proteins
  • Drosophila Proteins
  • Peptide Fragments
  • Recombinant Fusion Proteins
  • enhanced green fluorescent protein
  • jabba protein, Drosophila
  • Green Fluorescent Proteins
  • Casein Kinase II
  • CkIIalpha protein, Drosophila