Genome-wide screen identifies signaling pathways that regulate autophagy during Caenorhabditis elegans development.
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.
College of Life Sciences China Agricultural University, Beijing, China State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China National Institute of Biological Sciences, Beijing, China.
Bin
B
Guo
National Institute of Biological Sciences, Beijing, China.
Xinxin
X
Huang
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Peipei
P
Zhang
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Linxiang
L
Qi
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Qianqian
Q
Liang
National Institute of Biological Sciences, Beijing, China.
Xuebo
X
Zhang
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Jie
J
Huang
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Bin
B
Fang
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Wenru
W
Hou
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China.
Jinghua
J
Han
State Key Laboratory of Biomacromolecules, Institute of Biophysics Chinese Academy of Sciences, Beijing, China hongzhang@sun5.ibp.ac.cn.
Hong
H
Zhang
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000254:growth & development*; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000235:genetics*; D007413:Intestinal Mucosa / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D034622:RNA Interference; D012269:Ribosomal Proteins / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D046988:Proteasome Endopeptidase Complex; D012269:Ribosomal Proteins; D014157:Transcription Factors; C548052:ATFS-1 protein, C elegans; C583069:HLH-30 protein, C elegans; C000594450:RPL-43 protein, C elegans; C548541:XBP-1 protein, C elegans
Caenorhabditis elegans; ER stress; Rb; autophagy; mitochondrial stress