A secreted decoy of InR antagonizes insulin/IGF signaling to restrict body growth in Drosophila
- Laboratory for Growth Control Signaling, RIKEN Center for Developmental Biology (CDB), Chuo-ku, Hyogo, 466-8550 Japan
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.
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Footnotes
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↵1 Corresponding author
E-mail t-nishimura{at}cdb.riken.jp
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.204479.112.
- Received August 27, 2012.
- Accepted November 26, 2012.
- Copyright © 2013 by Cold Spring Harbor Laboratory Press