Gp78 regulates PMP22 and causes ER stress and autophagy in EV71-VP1-overexpressing mouse Schwann cells  

作　　者：DANPING ZHU GUANGMING LIU KUAN FENG SUYUN LI DANDAN HU SIDA YANG PEIQING LI 

机构地区：[1]Pediatric Emergency Department,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangdong Provincial Clinical Research Center for Child Health,Guangzhou,China [2]Department of Child Health Care,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangdong Provincial Clinical Research Center for Child Health,Guangzhou,China [3]Pediatric Neurology Department,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangdong Provincial Clinical Research Center for Child Health,Guangzhou,China

出　　处：《BIOCELL》2024年第4期653-664,共12页生物细胞（英文）

基　　金：The study was supported by Guangdong Natural Science Foundation(Grant Numbers 2020A1515010014,2022A1515012411);Science and Technology Key Project for People’s Livelihood of Guangzhou,China(Grant Number 202206010060);Guangzhou Science and Technology Bureau Basic Research Project(SL2024A03J01288);Innovative Project of Children’s Research Institute,Guangzhou Women and Children’s Medical Center,China(Grant Numbers Pre-NSFC-2019-002,NKE PRE-2019-015).

摘　　要：Background:During Enterovirus type 71(EV71)infection,the structural viral protein 1(VP1)activates endoplasmic reticulum(ER)stress associated with peripheral myelin protein 22(PMP22)accumulation and induces autophagy.However,the specific mechanism behind this process remains elusive.Methods:In this research,we used the VP1-overexpressing mouse Schwann cells(SCs)models co-transfected with a PMP22 silencing or Autocrine motility factor receptor(AMFR/gp78)overexpressing vector to explore the regulation of gp78 on PMP22 and its relationship with autophagy and apoptosis.Results:The activity of gp78 could be influenced by EV71-VP1,leading to a decrease in the ubiquitination and degradation of PMP22,resulting in PMP22 accumulation in ER.In VP1-overexpressing mouse SCs,all three ER stress sensors,including pancreatic endoplasmic reticulum kinase(PERK),activating transcription factor 6(ATF6)and inositol-requiring enzyme 1(IRE1)and the related downstream signals(C/EBP-homologous protein(CHOP)and Caspase 12)were activated,as well as the ER-resident chaperone Glucose-regulated protein 78(GRP78).In addition,VP1 upregulated the autophagy marker Microtubule-associated protein 1 light chain 3 beta(LC3B),while PMP22 silencing or gp78 overexpression reversed the phenomenon.Meanwhile,PMP22 silencing or gp78 overexpression increased proliferation of EV71-VP1-transfected mouse SCs.Conclusion:Gp78 could regulate PMP22 accumulation through ubiquitination degradation and cause ER stress and autophagy in EV71-VP1-overexpressing mouse SCs.Therefore,the gp78/PMP22/ER stress axis might emerge as a promising therapeutic target for myelin and neuronal damage induced by EV71 infection.

关 键 词：Enterovirus type 71 AMFR/gp78 PMP22 AUTOPHAGY Schwann cells 

分 类 号：R373[医药卫生—病原生物学]