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Open Access Highly Accessed Research article

Imp-L2, a putative homolog of vertebrate IGF-binding protein 7, counteracts insulin signaling in Drosophila and is essential for starvation resistance

Basil Honegger1, Milos Galic13, Katja Köhler2, Franz Wittwer1, Walter Brogiolo1, Ernst Hafen2* and Hugo Stocker2

Author Affiliations

1 Zoological Institute, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland

2 Institute for Molecular Systems Biology (IMSB), ETH Zürich, Wolfgang-Pauli-Strasse 16, CH-8093 Zürich, Switzerland

3 Current address: Chemical and Systems Biology, 318 Campus Drive, Clark Building W200, Stanford University Medical Center, Stanford, CA 94305-5174, USA

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Journal of Biology 2008, 7:10  doi:10.1186/jbiol72

Published: 15 April 2008

Abstract

Background

Insulin and insulin-like growth factors (IGFs) signal through a highly conserved pathway and control growth and metabolism in both vertebrates and invertebrates. In mammals, insulin-like growth factor binding proteins (IGFBPs) bind IGFs with high affinity and modulate their mitogenic, anti-apoptotic and metabolic actions, but no functional homologs have been identified in invertebrates so far.

Results

Here, we show that the secreted Imaginal morphogenesis protein-Late 2 (Imp-L2) binds Drosophila insulin-like peptide 2 (Dilp2) and inhibits growth non-autonomously. Whereas over-expressing Imp-L2 strongly reduces size, loss of Imp-L2 function results in an increased body size. Imp-L2 is both necessary and sufficient to compensate Dilp2-induced hyperinsulinemia in vivo. Under starvation conditions, Imp-L2 is essential for proper dampening of insulin signaling and larval survival.

Conclusion

Imp-L2, the first functionally characterized insulin-binding protein in invertebrates, serves as a nutritionally controlled suppressor of insulin-mediated growth in Drosophila. Given that Imp-L2 and the human tumor suppressor IGFBP-7 show sequence homology in their carboxy-terminal immunoglobulin-like domains, we suggest that their common precursor was an ancestral insulin-binding protein.