[Frontiers In Bioscience, Landmark, 23, 2016-2027, June1, 2018]
Regulation of feeding behavior in Drosophila through the interplay of gustation, physiology and neuromodulation
Figure 1. Insulin/TOR signaling pathway in Drosophila: The Drosophila insulin like peptides (DILPs 1-8) released from several sites all over the body acts on Drosophila insulin like receptor (dInR) and initiates a signaling cascade. The cascade involves activation of insulin receptor substrate Chico, Phosphatidylinositide 3-Kinase (PI3K) and subsequent conversion of Phosphatidylinositol 4, 5 bisphosphate (PIP2) to Phosphatidylinositol (3, 4, 5) - triphosphate (PIP3) for activation of Protein Kinase B (PKB)/ Akt. The phosphatase and tensin homolog (PTEN) inhibits the action of PI3K. The Akt in normal nutritional situation inhibits Forkhead Box class O (dFoxo) transcription factor thereby promoting cell growth. In case of nutritional deficiency dFoxo gets activated and in turn activate 4E- Binding Protein (4E-BP) which is a translational repressor. Akt also inhibits Tuberous Sclerosis Complex 1 and 2 (TSC 1 and 2) and Ras homolog enriched in brain (Rheb) which negatively regulate Target of Rapamycin (TOR) pathway. The presence of high intracellular amino acids (AA) activates Rheb and finally TOR complex. dTOR stimulates protein synthesis by activating ribosomal protein S6 kinase (dS6K) and Transcription intermediary factor 1A (TIF-1A).
Figure 2. Interaction of Insulin/ TOR signaling pathway (described in Figure 1) and Neuropeptide F (NPF) in feeding decision process. In well-fed condition the intrinsic stable metabolic state inhibits the hunger stimuli. High insulin signaling and increased level of dS6K and DILPs activity inhibit the huger driven feeding in Drosophila larvae. In case of hunger stimuli, the dS6K activity is downregulated and henceforth insulin signaling, thereby promoting Neuropeptide F mediated motivated feeding.
Figure 3. Gustatory perception, Neuromodulation and Insulin signaling aids in the final feeding process