TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth

TY - JOUR

T1 - TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth

AU - Hennig, Krista M

AU - Colombani, Julien

AU - Neufeld, Thomas P

PY - 2006/6/19

Y1 - 2006/6/19

N2 - 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.

AB - 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.

KW - Amino Acid Transport Systems/metabolism

KW - Animals

KW - Cell Enlargement

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/cytology

KW - Endocytosis/physiology

KW - Fat Body/cytology

KW - HSC70 Heat-Shock Proteins/genetics

KW - Models, Biological

KW - Phenotype

KW - Phosphatidylinositol 3-Kinases/physiology

KW - Protein Kinases

KW - Signal Transduction

KW - TOR Serine-Threonine Kinases

U2 - 10.1083/jcb.200511140

DO - 10.1083/jcb.200511140

M3 - Journal article

C2 - 16785324

SN - 0021-9525

VL - 173

SP - 963

EP - 974

JO - Journal of Cell Biology

JF - Journal of Cell Biology

IS - 6

ER -