A Nutrient Sensor Mechanism Controls Drosophila Growth

Abstract

Organisms modulate their growth according to nutrient availability. Although individual cells in a multicellular animal may respond directly to nutrient levels, growth of the entire organism needs to be coordinated. Here, we provide evidence that in Drosophila, coordination of organismal growth originates from the fat body, an insect organ that retains endocrine and storage functions of the vertebrate liver. In a genetic screen for growth modifiers, we identified slimfast, a gene that encodes an amino acid transporter. Remarkably, downregulation of slimfast specifically within the fat body causes a global growth defect similar to that seen in Drosophila raised under poor nutritional conditions. This involves TSC/TOR signaling in the fat body, and a remote inhibition of organismal growth via local repression of PI3-kinase signaling in peripheral tissues. Our results demonstrate that the fat body functions as a nutrient sensor that restricts global growth through a humoral mechanism.

Stress and mTORture signaling

“…Similarly, ablation of insulinproducing neurons in the Drosophila brain engenders a systemic growth defect, resulting in the generation of small flies with elevated carbohydrate levels (Ikeya et al, 2002;Rulifson et al, 2002). Colombani et al (2003) found that reducing dTOR signaling in the fat body led to a pronounced downregulation of insulin pathway activity in peripheral tissues generating smaller-sized flies. Non-autonomous mTOR-dependent effects also exist in mammals.…”

Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression

“…Not only does TOR control cell growth in a cell autonomous manner, but a new publication suggests that dTOR in Drosophila may control cell growth by a non cell autonomous, humoral mechanism (Colombani et al, 2003): mutation of dTOR, mutation of an aminoacid transporter known as slimfast, or overexpression of TSC1/2 in an organ called the fat body affects the growth of other tissues. The authors propose a model whereby the fat body secretes a signal via a TOR-and S6K-dependent mechanism that is sensed by peripheral tissues.…”

Methods to study Drosophila immunity

“…This insertion lowers the viability of flies and as a consequence, yolk-Gal4 stocks are usually kept at 23°C. The strength of the driver may be influenced by nutritional state w; P{GawB}c564 BL6982 The c564 driver strongly expresses Gal4 in the adult fat body (and in parts of the gut and hemocytes) P{ppl-GAL4.P} [124] The ppl-Gal4 driver strongly expresses Gal4 in the larval and adult fat body (and also in the gut). It is weaker than c564 at the adult stage…”