A functional interaction between TDP-43 and USP10 reveals USP10 dysfunction in TDP-43 proteinopathies

Author:

Marrero-Gagliardi A,Noda JORCID,Zanovello M,Brito Armas JM,Bampton A,Torres P,Pérez Hernández C,Fumagallo F,Taoro L,Muñoz de Bustillo Alfaro R,Brown AL,Quinet G,Andrés-Benito PORCID,Ferrer I,Acebes A,Freire R,Smits VAJ,Keuss M,Portero-Otin M,Lashley T,Fratta P,Acevedo-Arozena AORCID

Abstract

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive degeneration of motor neurons in the cerebral cortex and spinal cord, with a rapid progression from diagnosis to death. The great majority of ALS cases and around 50% of FTD cases present with TDP-43 pathology, leading to mislocalization and cytoplasmic aggregation of TDP-43, which can result in both its loss of nuclear functions and a gain of toxicity in the cytoplasm. TDP-43 and other RNA-binding proteins accumulate in stress granules (SGs) under stress conditions. The ubiquitin-specific protease 10 (USP10) is an inhibitor of SGs assembly that has been recently linked to neurodegeneration. Here, we identified a new functional interaction between TDP-43 and USP10, in which USP10 can control multiple aspects of TDP-43 biology that are thought to play important roles in its involvement in disease pathogenesis, such as its cytoplasmic and nuclear aggregation, expression and splicing functionality. In turn, TDP-43 is also able to control diverse aspects of USP10 biology, such as its expression levels, aggregation and function. Critically, we found USP10 dysregulation in ALS and FTD patients, overall suggesting a possible role for USP10 in ALS/FTD pathogenesis.

Publisher

Cold Spring Harbor Laboratory

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3