Loss of VAPB Regulates Autophagy in a Beclin 1-Dependent Manner  

作　　者：Dan Wu Zongbing Hao Haigang Ren Guanghui Wang 

机构地区：[1]Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University

出　　处：《Neuroscience Bulletin》2018年第6期1037-1046,共10页神经科学通报（英文版）

基　　金：supported in part by the National Key R&D Program of China (2016YFC1306000);the National Natural Sciences Foundation of China (31330030, 31471012, and 81761148024);a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions

摘　　要：Autophagy is an evolutionarily-conserved selfdegradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles.Recently, vesicle-associated membrane protein-associated protein B(VAPB), which is associated with the familial form of amyotrophic lateral sclerosis, has been shown to regulate autophagy. In the present study, we demonstrated that knockdown of VAPB induced the up-regulation of beclin 1 expression, which promoted LC3(microtubuleassociated protein light chain 3) conversion and the formation of LC3 puncta, whereas overexpression of VAPB inhibited these processes. The regulation of beclin1 by VAPB was at the transcriptional level. Moreover,knockdown of VAPB increased autophagic flux, which promoted the degradation of the autophagy substrate p62 and neurodegenerative disease proteins. Our study provides evidence that the regulation of autophagy by VAPB is associated with the autophagy-initiating factor beclin 1.Autophagy is an evolutionarily-conserved selfdegradative process that maintains cellular homeostasis by eliminating protein aggregates and damaged organelles.Recently, vesicle-associated membrane protein-associated protein B(VAPB), which is associated with the familial form of amyotrophic lateral sclerosis, has been shown to regulate autophagy. In the present study, we demonstrated that knockdown of VAPB induced the up-regulation of beclin 1 expression, which promoted LC3(microtubuleassociated protein light chain 3) conversion and the formation of LC3 puncta, whereas overexpression of VAPB inhibited these processes. The regulation of beclin1 by VAPB was at the transcriptional level. Moreover,knockdown of VAPB increased autophagic flux, which promoted the degradation of the autophagy substrate p62 and neurodegenerative disease proteins. Our study provides evidence that the regulation of autophagy by VAPB is associated with the autophagy-initiating factor beclin 1.

关 键 词：VAPB AUTOPHAGY Beclin 1 ALS Autophagic flux LC3 

分 类 号：R[医药卫生]