Cyclin G Functions as a Positive Regulator of Growth and Metabolism in Drosophila.
In multicellular organisms, growth and proliferation is adjusted to nutritional conditions by a complex signaling network. The Insulin receptor/target of rapamycin (InR/TOR) signaling cascade plays a pivotal role in nutrient dependent growth regulation in Drosophila and mammals alike. Here we identify Cyclin G (CycG) as a regulator of growth and metabolism in Drosophila. CycG mutants have a reduced body size and weight and show signs of starvation accompanied by a disturbed fat metabolism. InR/TOR signaling activity is impaired in cycG mutants, combined with a reduced phosphorylation status of the kinase Akt1 and the downstream factors S6-kinase and eukaryotic translation initiation factor 4E binding protein (4E-BP). Moreover, the expression and accumulation of Drosophila insulin like peptides (dILPs) is disturbed in cycG mutant brains. Using a reporter assay, we show that the activity of one of the first effectors of InR signaling, Phosphoinositide 3-kinase (PI3K92E), is unaffected in cycG mutants. However, the metabolic defects and weight loss in cycG mutants were rescued by overexpression of Akt1 specifically in the fat body and by mutants in widerborst (wdb), the B'-subunit of the phosphatase PP2A, known to downregulate Akt1 by dephosphorylation. Together, our data suggest that CycG acts at the level of Akt1 to regulate growth and metabolism via PP2A in Drosophila.
Institute of Genetics, University of Hohenheim, Stuttgart, Germany.
Patrick
P
Fischer
Institute of Genetics, University of Hohenheim, Stuttgart, Germany.
Martina K
MK
La Rosa
Institute of Genetics, University of Hohenheim, Stuttgart, Germany.
Adriana
A
Schulz
Institute of Genetics, University of Hohenheim, Stuttgart, Germany.
Anette
A
Preiss
Institute of Genetics, University of Hohenheim, Stuttgart, Germany.
Anja C
AC
Nagel
D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism; D056746:Cyclin G / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D005216:Fat Body / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D050356:Lipid Metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism
D056746:Cyclin G; C111892:DIAP2 protein, Drosophila; D029721:Drosophila Proteins; D051034:Inhibitor of Apoptosis Proteins; C494917:Akt1 protein, Drosophila; D051057:Proto-Oncogene Proteins c-akt; D010749:Phosphoprotein Phosphatases; C079898:tws protein, Drosophila