The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila

作者: Gábor Juhász , Jahda H. Hill , Ying Yan , Miklós Sass , Eric H. Baehrecke

DOI: 10.1083/JCB.200712051

关键词:

摘要: Degradation of cytoplasmic components by autophagy requires the class III phosphatidylinositol 3 (PI(3))-kinase Vps34, but mechanisms which this kinase and its lipid product PI(3) phosphate (PI(3)P) promote are unclear. In mammalian cells, with proautophagic tumor suppressors Beclin1/Atg6, Bif-1, UVRAG, forms a multiprotein complex that initiates autophagosome formation. Distinct Vps34 complexes also regulate endocytic processes critical for late-stage autophagosome-lysosome fusion. contrast, may transduce activating nutrient signals to target rapamycin (TOR), negative regulator autophagy. To determine potential in vivo functions we generated mutations single Drosophila melanogaster orthologue, causing cell-autonomous disruption autophagosome/autolysosome formation larval fat body cells. Endocytosis is disrupted Vps34(-/-) animals, demonstrate does not account their defect. Unexpectedly, TOR signaling unaffected mutants, indicating act upstream system. Instead, show TOR/Atg1 regulates starvation-induced recruitment PI(3)P nascent autophagosomes. Our results suggest regulated TOR-dependent directly at sites

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