Haploinsufficiency oftheTDP43 ubiquitin E3 ligase RNF220 leads to ALS-like motor neuron defects in the mouse  

作　　者：Pengcheng Ma Yuwei Li Huishan Wang Bingyu Mao 

机构地区：[1]State Key Laboratory of Genetic Resources and Evolution,Kunming Institute of Zoology,Chinese Academy of Sciences,Kunming 650223,China [2]Kunming College of Life Science,University of Chinese Academy of Sciences,Kunming 650203,China [3]Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming 650223,China

出　　处：《Journal of Molecular Cell Biology》2021年第5期374-382,共9页分子细胞生物学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31671521 and 31871483 to B.M.);Yunnan Basic Research Program(202001AS070036 to B.M.).

摘　　要：TDP43 pathology is seen in a large majority of amyotrophic lateral sclerosis(ALS)cases,suggesting a central pathogenic role of this regulatory protein.Clarifying the molecular mechanism controlling TDP43 stability and subcellular location might provide important insights into ALS therapy.The ubiquitin E3 ligase RNF220 is involved in different neural developmental processes through various molecular targets in the mouse.Here,we report that the RNF2207 mice showed progressively decreasing mobility to different extents,some of which developed typical ALS pathological characteristics in spinal motor neurons,including TDP43 cytoplasmic accumulation,atrocytosis,muscle denervation,and atrophy.Mechanistically,RNF220 interacts with TDP43 in vitro and in vivo and promotes its polyubiquitination and proteasomal degradation.In conclusion,we propose that RNF220 might be a modifier of TDP43 function in vivo and contribute to TDP43 pathology in neurodegenerative disease like ALS.

关 键 词：TDP43 RNF220 amyotrophic lateral sclerosis(ALS) POLYUBIQUITINATION 

分 类 号：Q2[生物学—细胞生物学] Q421