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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
Affiliation:1College of Life Sciences, China AgriculturalUniversity, Beijing, China;2State Key Laboratory of Biomacromolecules, Institute ofBiophysics, 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 duringmulticellular organism development remain largely unknown. Here, we show that impaired function ofribosomal protein RPL-43 causes an accumulation of SQST-1 aggregates in the larval intestine, whichare removed upon autophagy induction. Using this model to screen for autophagy regulators, weidentify 139 genes that promote autophagy activity upon inactivation. Various signaling pathways,including Sma/Mab TGF-β signaling, lin-35/Rb signaling, the XBP-1-mediatedER stress response, and the ATFS-1-mediated mitochondrial stress response, regulate the expressionof autophagy genes independently of the TFEB homolog HLH-30. Our study thus provides a framework forunderstanding the role of signaling pathways in regulating autophagy under physiologicalconditions.Subject Categories: Autophagy & Cell Death; Signal Transduction; Membrane & Intracellular Transport
Keywords:autophagy   Caenorhabditis elegans   ER stress   mitochondrial stress   Rb
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