气候变化领域集成服务门户(CCPortal): The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics

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DOI	10.1073/pnas.2011379118
	The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics
	Luo S.; Wang X.; Bai M.; Jiang W.; Zhang Z.; Chen Y.; Ma D.K.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	TMEM39A encodes an evolutionarily conserved transmembrane protein and carries single-nucleotide polymorphisms associated with increased risk of major human autoimmune diseases, including multiple sclerosis. The exact cellular function of TMEM39A remains not well understood. Here, we report that TMEM-39, the sole Caenorhabditis elegans (C. elegans) ortholog of TMEM39A, regulates lysosome distribution and accumulation. Elimination of tmem-39 leads to lysosome tubularization and reduced lysosome mobility, as well as accumulation of the lysosome-associated membrane protein LMP-1. In mammalian cells, loss of TMEM39A leads to redistribution of lysosomes from the perinuclear region to cell periphery. Mechanistically, TMEM39A interacts with the dynein intermediate light chain DYNC1I2 to maintain proper lysosome distribution. Deficiency of tmem-39 or the DYNC1I2 homolog in C. elegans impairs mTOR signaling and activates the downstream TFEB-like transcription factor HLH-30. We propose evolutionarily conserved roles of TMEM39 family proteins in regulating lysosome distribution and lysosome-associated signaling, dysfunction of which in humans may underlie aspects of autoimmune diseases. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoimmune disorders; Autoimmunity; Dynein; Lysosome; TMEM39A
语种	英语
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/180720
作者单位	Cardiovascular Research Institute, University of California, San Francisco, CA 94158, United States; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, United States; Department of Physiology, University of California, San Francisco, CA 94158, United States
推荐引用方式 GB/T 7714	Luo S.,Wang X.,Bai M.,et al. The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics[J],2021,118(6).
APA	Luo S..,Wang X..,Bai M..,Jiang W..,Zhang Z..,...&Ma D.K..(2021).The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Luo S.,et al."The conserved autoimmune-disease risk gene TMEM39A regulates lysosome dynamics".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).