A Multicomponent Neuronal Response Encodes the Larval Decision to Pupariate upon Amino Acid Starvation

J Neurosci. 2018 Nov 21;38(47):10202-10219. doi: 10.1523/JNEUROSCI.1163-18.2018. Epub 2018 Oct 9.


Organisms need to coordinate growth with development, particularly in the context of nutrient availability. Thus, multiple ways have evolved to survive extrinsic nutrient deprivation during development. In Drosophila, growth occurs during larval development. Larvae are thus critically dependent on nutritional inputs; but after critical weight, they pupariate even when starved. How nutrient availability is coupled to the internal metabolic state for the decision to pupariate needs better understanding. We had earlier identified glutamatergic interneurons in the ventral ganglion that regulate pupariation on a protein-deficient diet. Here we report that Drosophila third instar larvae (either sex) sense arginine to evaluate their nutrient environment using an amino acid transporter Slimfast. The glutamatergic interneurons integrate external protein availability with internal metabolic state through neuropeptide signals. IP3-mediated calcium release and store-operated calcium entry are essential in these glutamatergic neurons for such integration and alter neuronal function by reducing the expression of multiple ion channels.SIGNIFICANCE STATEMENT Coordinating growth with development, in the context of nutrient availability is a challenge for all organisms in nature. After attainment of "critical weight," insect larvae can pupariate, even in the absence of nutrition. Mechanism(s) that stimulate appropriate cellular responses and allow normal development on a nutritionally deficient diet remain to be understood. Here, we demonstrate that nutritional deprivation, in postcritical weight larvae, is sensed by special sensory neurons through an amino acid transporter that detects loss of environmental arginine. This information is integrated by glutamatergic interneurons with the internal metabolic state through neuropeptide signals. These glutamatergic interneurons require calcium-signaling-regulated expression of a host of neuronal channels to generate complex calcium signals essential for pupariation on a protein-deficient diet.

Keywords: Drosophila; SOCE; glutamatergic neurons; nutrient-sensing.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acids / deficiency
  • Animals
  • Animals, Genetically Modified
  • Arginine / deficiency*
  • Diet, Protein-Restricted / trends*
  • Drosophila
  • Female
  • Interneurons / metabolism*
  • Larva / growth & development
  • Larva / metabolism*
  • Male
  • Pupa / growth & development
  • Pupa / metabolism*
  • Sensory Receptor Cells / metabolism*


  • Amino Acids
  • Arginine