Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila

doi:10.1073/pnas.0501914102

Regulation of hunger-driven behaviors by neural ribosomal S6 kinase in Drosophila

Department of Cellular Biology, and Biomedical and Health Sciences Institute, University of Georgia, 724 Biological Sciences Building, Athens, GA 30602

Edited by Cornelia I. Bargmann, The Rockefeller University, New York, NY (received for review March 8, 2005)

Abstract

Hunger elicits diverse, yet coordinated, adaptive responses across species, but the underlying signaling mechanism remains poorly understood. Here, we report on the function and mechanism of the Drosophila insulin-like system in the central regulation of different hunger-driven behaviors. We found that overexpression of Drosophila insulin-like peptides (DILPs) in the nervous system of fasted larvae suppressed the hunger-driven increase of ingestion rate and intake of nonpreferred foods (e.g., a less accessible solid food). Moreover, up-regulation of Drosophila p70/S6 kinase activity in DILP neurons led to attenuated hunger response by fasted larvae, whereas its down-regulation triggered fed larvae to display motivated foraging and feeding. Finally, we provide evidence that neural regulation of food preference but not ingestion rate may involve direct signaling by DILPs to neurons expressing neuropeptide F receptor 1, a receptor for neuropeptide Y-like neuropeptide F. Our study reveals a prominent role of neural Drosophila p70/S6 kinase in the modulation of hunger response by insulin-like and neuropeptide Y-like signaling pathways.

Footnotes

↵ * To whom correspondence should be addressed. E-mail: pshen{at}cellmate.cb.uga.edu.
Author contributions: P.S. designed research; Q.W., Y.Z., and J.X. performed research; P.S. contributed new reagents/analytic tools; Q.W. and P.S. analyzed data; and Q.W. and P.S. wrote the paper.
This paper was submitted directly (Track II) to the PNAS office.
Abbreviations: dS6k, Drosophila p70/S6 kinase; dInR, Drosophila insulin receptor; NPY, neuropeptide Y; NPF, neuropeptide F; NPFR, NPF receptor; DILP, Drosophila insulin-like peptide; PTEN, phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase; PI3K, phosphatidylinositol 3-kinase.