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

Megha Megha,Gaiti Hasan

doi:10.1242/dev.145235

Abstract

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.

Highlights

Nutritional poverty during development has long-lasting effects on growth and behavior of an animal
As neuropeptides secreted by neuroendocrine (NE) cells critically modulate neural circuits, we investigated NE cell function during development under nutrient stress
An IP3R (Inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by over-expression of either insulin receptor (InR) or IP3R in NE cells of the mutant, suggesting that the two signaling pathways may be functionally compensatory

Summary

Introduction

Nutritional poverty during development has long-lasting effects on growth and behavior of an animal. Under-nutrition causes overall body size to decrease, the brain grows to near-normal size, a process termed “Brain Sparing” (Dobbing and Sands, 1971). Adults of a hypomorphic IP3R mutant heteroallelic combination, itprka1091/ug (hereafter: itprku) exhibit obesity, starvation resistance and hyperphagia, which are all rescued by over-expression of IP3R in NE cells (Subramanian et al, 2013a). This adult metabolic phenotype prompted an investigation on a role for IP3R and InR in NE cells, during larval development

Results and Discussion

Materials and methods

Experimental Procedure