气候变化领域集成服务门户(CCPortal): Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling

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DOI	10.1073/pnas.2101410118
	Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling
	Cooper J.F.; Guasp R.J.; Arnold M.L.; Grant B.D.; Driscoll M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:36
英文摘要	In human neurodegenerative diseases, neurons can transfer toxic protein aggregates to surrounding cells, promoting pathology via poorly understood mechanisms. In Caenorhabditis elegans, proteostressed neurons can expel neurotoxic proteins in large, membrane-bound vesicles called exophers. We investigated how specific stresses impact neuronal trash expulsion to show that neuronal exopher production can be markedly elevated by oxidative and osmotic stress. Unexpectedly, we also found that fasting dramatically increases exophergenesis. Mechanistic dissection focused on identifying nonautonomous factors that sense and activate the fasting-induced exopher response revealed that DAF16/FOXOdependent and -independent processes are engaged. Fasting-induced exopher elevation requires the intestinal peptide transporter PEPT-1, lipid synthesis transcription factors Mediator complex MDT-15 and SBP-1/SREPB1, and fatty acid synthase FASN-1, implicating remotely initiated lipid signaling in neuronal trash elimination. A conserved fibroblast growth factor (FGF)/RAS/MAPK signaling pathway that acts downstream of, or in parallel to, lipid signaling also promotes fasting-induced neuronal exopher elevation. A germline-based epidermal growth factor (EGF) signal that acts through neurons is also required for exopher production. Our data define a nonautonomous network that links food availability changes to remote, and extreme, neuronal homeostasis responses relevant to aggregate transfer biology. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Exopher; Fasting; MAP kinase; Neurology; Stress
语种	英语
scopus关键词	epidermal growth factor; fatty acid synthase; fibroblast growth factor; lipid; mediator complex; mitogen activated protein kinase; peptide transporter 1; protein MDT 15; protein SBP 1; protein SREPB1; Ras protein; transcription factor; transcription factor DAF 16; transcription factor FOXO; unclassified drug; aging; animal cell; animal experiment; Article; cell vacuole; cellular, subcellular and molecular biological phenomena and functions; controlled study; exopher; exophergenesis; fasting; food availability; food quality; hypoxia; lipid signaling; mouse; nerve degeneration; neurology; nonhuman; osmotic stress; oxidative stress; physiological stress; temperature stress
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238807
作者单位	Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, United States; Rutgers Center for Lipid Research, Rutgers University, New Brunswick, NJ 08901, United States
推荐引用方式 GB/T 7714	Cooper J.F.,Guasp R.J.,Arnold M.L.,et al. Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling[J],2021,118(36).
APA	Cooper J.F.,Guasp R.J.,Arnold M.L.,Grant B.D.,&Driscoll M..(2021).Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling.Proceedings of the National Academy of Sciences of the United States of America,118(36).
MLA	Cooper J.F.,et al."Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling".Proceedings of the National Academy of Sciences of the United States of America 118.36(2021).