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Genome-wide screen identifies signaling pathways that regulate autophagy during Caenorhabditis elegans development
Authors:Bin Guo  Xinxin Huang  Peipei Zhang  Linxiang Qi  Qianqian Liang  Xuebo Zhang  Jie Huang  Bin Fang  Wenru Hou  Jinghua Han  Hong Zhang
Institution:1College of Life Sciences, China Agricultural University, Beijing, China;2State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China;3National Institute of Biological Sciences, Beijing, China
Abstract:The mechanisms that coordinate the regulation of autophagy with developmental signaling during multicellular organism development remain largely unknown. Here, we show that impaired function of ribosomal protein RPL-43 causes an accumulation of SQST-1 aggregates in the larval intestine, which are removed upon autophagy induction. Using this model to screen for autophagy regulators, we identify 139 genes that promote autophagy activity upon inactivation. Various signaling pathways, including Sma/Mab TGF-β signaling, lin-35/Rb signaling, the XBP-1-mediated ER stress response, and the ATFS-1-mediated mitochondrial stress response, regulate the expression of autophagy genes independently of the TFEB homolog HLH-30. Our study thus provides a framework for understanding the role of signaling pathways in regulating autophagy under physiological conditions.Subject Categories: Autophagy & Cell Death; Signal Transduction; Membrane & Intracellular Transport
Keywords:autophagy  Caenorhabditis elegans  ER stress  mitochondrial stress  Rb
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