TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth.
TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth.
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DOI：
10.1083/jcb.200511140
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发表时间：
2006-06-19
影响因子：
7.8
通讯作者：
Neufeld, Thomas P
中科院分区：
文献类型：
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作者：
Hennig, Krista M;Colombani, Julien;Neufeld, Thomas P
雷帕霉素靶蛋白（TOR）是细胞和生物体响应营养条件生长的中心调节因子。在一个新的TOR相互作用在果蝇的遗传筛选中，我们已经确定了网格蛋白未涂层ATP酶Hsc 70 -4，这是一个关键的调节内吞作用。我们提出的遗传证据表明，TOR信号刺激大量内吞摄取，并抑制有针对性的内吞降解的氨基酸进口商Slimfast。因此，TOR同时下调抑制生长的内吞作用的方面，并上调内吞作用的潜在促生长功能。此外，我们发现内吞作用的破坏导致TOR和磷脂酰肌醇-3激酶活性的变化，影响细胞生长，自噬和雷帕霉素敏感性。我们的数据表明，内吞作用作为效应器功能下游的TOR和作为生理相关的调节TOR信号。
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.