Two-tiered control of epithelial growth and autophagy by the insulin receptor and the ret-like receptor, stitcher

PLoS Biol. 2013 Jul;11(7):e1001612. doi: 10.1371/journal.pbio.1001612. Epub 2013 Jul 23.

Abstract

Body size in Drosophila larvae, like in other animals, is controlled by nutrition. Nutrient restriction leads to catabolic responses in the majority of tissues, but the Drosophila mitotic imaginal discs continue growing. The nature of these differential control mechanisms that spare distinct tissues from starvation are poorly understood. Here, we reveal that the Ret-like receptor tyrosine kinase (RTK), Stitcher (Stit), is required for cell growth and proliferation through the PI3K-I/TORC1 pathway in the Drosophila wing disc. Both Stit and insulin receptor (InR) signaling activate PI3K-I and drive cellular proliferation and tissue growth. However, whereas optimal growth requires signaling from both InR and Stit, catabolic changes manifested by autophagy only occur when both signaling pathways are compromised. The combined activities of Stit and InR in ectodermal epithelial tissues provide an RTK-mediated, two-tiered reaction threshold to varying nutritional conditions that promote epithelial organ growth even at low levels of InR signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Ectoderm / cytology
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Drosophila Proteins
  • Receptor, Insulin

Grant support

This work was supported by the Swedish Cancer Society (Cancerfonden), the Swedish Research Council (VR), the Norwegian Cancer Society (TE), and the Norwegian Research Council Centre of Excellence programme (FOF, awarded to Harald Stenmark). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.