title: A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila.
abstract: Members of the insulin peptide family have conserved roles in the regulation of growth and metabolism in a wide variety of metazoans. Drosophila insulin-like peptides (Dilps) promote tissue growth through the single insulin-like receptor (InR). Despite the important role of Dilps in nutrient-dependent growth control, the molecular mechanism that regulates the activity of circulating Dilps is not well understood. Here, we report the function of a novel secreted decoy of InR (SDR) as a negative regulator of insulin signaling. SDR is predominantly expressed in glia and is secreted into the hemolymph. Larvae lacking SDR grow at a faster rate, thereby increasing adult body size. Conversely, overexpression of SDR reduces body growth non-cell-autonomously. SDR is structurally similar to the extracellular domain of InR and interacts with several Dilps in vitro independent of Imp-L2, the ortholog of the mammalian insulin-like growth factor-binding protein 7 (IGFBP7). We further demonstrate that SDR is constantly secreted into the hemolymph independent of nutritional status and is essential for adjusting insulin signaling under adverse food conditions. We propose that Drosophila uses a secreted decoy to fine-tune systemic growth against fluctuations of circulating insulin levels.
authors: Laboratory for Growth Control Signaling, RIKEN Center for Developmental Biology, Chuo-ku, Hyogo, Japan.
authors: Naoki
authors: N
authors: Okamoto
authors: Rinna
authors: R
authors: Nakamori
authors: Tomoka
authors: T
authors: Murai
authors: Yuki
authors: Y
authors: Yamauchi
authors: Aya
authors: A
authors: Masuda
authors: Takashi
authors: T
authors: Nishimura
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000254:growth & development* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006458:Hemolymph / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007814:Larva; D009457:Neuroglia / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D007328:Insulin; D013002:Somatomedins; C094982:InR protein, Drosophila; D020794:Receptor Protein-Tyrosine Kinases