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Updated: Aug 7, 2026
Analyzing Starvation-Induced Autophagy in the Drosophila melanogaster Larval Fat Body
Published on: August 4, 2022
TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth
Krista M Hennig1, Julien Colombani, Thomas P Neufeld
1Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
Abstract:
Target of rapamycin (TOR) is a central regulator of cellular and organismal growth in response to nutrient conditions. In a genetic screen for novel TOR interactors in Drosophila melanogaster, we have identified the clathrin-uncoating ATPase Hsc70-4, which is a key regulator of endocytosis. We present genetic evidence that TOR signaling stimulates bulk endocytic uptake and inhibits the targeted endocytic degradation of the amino acid importer Slimfast. Thus, TOR simultaneously down-regulates aspects of endocytosis that inhibit growth and up-regulates potential growth-promoting functions of endocytosis. In addition, we find that disruption of endocytosis leads to changes in TOR and phosphatidylinositol-3 kinase activity, affecting cell growth, autophagy, and rapamycin sensitivity. Our data indicate that endocytosis acts both as an effector function downstream of TOR and as a physiologically relevant regulator of TOR signaling.
Insights
The target of rapamycin (TOR) pathway regulates cell growth by influencing endocytosis. This study reveals TOR signaling impacts bulk endocytosis and amino acid importer degradation, highlighting a reciprocal relationship between TOR and endocytosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The target of rapamycin (TOR) pathway is a critical regulator of cell growth, responding to nutrient availability.
- Endocytosis is a fundamental cellular process involved in nutrient uptake and signal transduction.
Purpose of the Study:
- To identify novel interactors of TOR signaling in Drosophila melanogaster.
- To elucidate the role of TOR signaling in regulating endocytosis and its impact on cell growth.
Main Methods:
- Genetic screening in Drosophila melanogaster to identify TOR interactors.
- Analysis of endocytic pathways and their regulation by TOR signaling.
- Investigating the effects of endocytosis disruption on TOR pathway activity.
Main Results:
- Hsc70-4, a clathrin-uncoating ATPase, was identified as a novel TOR interactor.
- TOR signaling stimulates bulk endocytosis and inhibits the degradation of the amino acid importer Slimfast.
- Disruption of endocytosis affects TOR and phosphatidylinositol-3 kinase activity, influencing cell growth, autophagy, and rapamycin sensitivity.
Conclusions:
- Endocytosis functions as both a downstream effector of TOR signaling and a regulator of TOR activity.
- TOR signaling modulates endocytosis to balance growth inhibition and promotion.
- A reciprocal regulatory loop exists between TOR signaling and endocytosis in cellular processes.
