IP3R-mediated Ca2+ release regulates protein metabolism in Drosophila neuroendocrine cells: implications for development under nutrient stress

Development. 2017 Apr 15;144(8):1484-1489. doi: 10.1242/dev.145235. Epub 2017 Mar 13.


Successful completion of animal development is fundamentally reliant on nutritional cues. Surviving periods of nutritional insufficiency requires adaptations that are coordinated, in part, by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation if either insulin signaling or IP3/Ca2+ signaling were downregulated in NE cells. Moreover, an IP3R (inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by overexpression of either InR (insulin receptor) or IP3R in NE cells of the mutant, suggesting that the two signaling pathways might be functionally compensatory. Furthermore, cultured IP3R mutant NE cells, but not neurons, exhibited reduced protein translation. Thus cell-specific regulation of protein synthesis by IP3R in NE cells influences protein metabolism. We propose that this regulation helps developing animals survive in poor nutritional conditions.

Keywords: ER Ca2+ stores; Insulin signaling; Pupariation; Starvation; dILP5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling / drug effects
  • Down-Regulation / drug effects
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / drug effects
  • Drosophila melanogaster / embryology*
  • Drosophila melanogaster / metabolism*
  • Food
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism*
  • Intracellular Space / metabolism
  • Larva / drug effects
  • Larva / growth & development
  • Mutation / genetics
  • Neuroendocrine Cells / cytology*
  • Neuroendocrine Cells / metabolism*
  • Protein Biosynthesis / drug effects
  • Pupa / drug effects
  • Pupa / growth & development
  • Receptor, Insulin / metabolism
  • Stress, Physiological* / drug effects
  • Sucrose / pharmacology


  • Inositol 1,4,5-Trisphosphate Receptors
  • Sucrose
  • Receptor, Insulin
  • Calcium