TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth
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TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. / Hennig, Krista M; Colombani, Julien; Neufeld, Thomas P.
In: The Journal of Cell Biology, Vol. 173, No. 6, 19.06.2006, p. 963-74.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 173
SP - 963
EP - 974
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -
ID: 213553088