TY  - EJOU
AU  - ZHU, DANPING 
AU  - LIU, GUANGMING 
AU  - FENG, KUAN 
AU  - LI, SUYUN 
AU  - HU, DANDAN 
AU  - YANG, SIDA 
AU  - LI, PEIQING 

TI  - Gp78 regulates PMP22 and causes ER stress and autophagy in EV71-VP1-overexpressing mouse Schwann cells
T2  - BIOCELL

PY  - 2024
VL  - 48
IS  - 4
SN  - 1667-5746

AB  -  <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusion:</b> 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.
KW  - Enterovirus type 71; AMFR/gp78; PMP22; Autophagy; Schwann cells

DO  - 10.32604/biocell.2024.044856