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Endoplasmic reticulum associated degradation is required for maintaining endoplasmic reticulum homeostasis and viability of mature Schwann cells in adults
Author(s) -
Wu Shuangchan,
Stone Sarrabeth,
Yue Yuan,
Lin Wensheng
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23910
Subject(s) - endoplasmic reticulum , endoplasmic reticulum associated protein degradation , unfolded protein response , microbiology and biotechnology , biology , homeostasis
The integrated unfolded protein response (UPR) and endoplasmic reticulum associated degradation (ERAD) is the principle mechanisms that maintain endoplasmic reticulum (ER) homeostasis. Schwann cells (SCs) must produce an enormous amount of myelin proteins via the ER to assemble and maintain myelin structure; however, it is unclear how SCs maintain ER homeostasis. It is known that Suppressor/Enhancer of Lin‐12‐like (Sel1L) is necessary for the ERAD activity of the Sel1L‐ hydroxymethylglutaryl reductase degradation protein 1(Hrd1) complex. Herein, we showed that Sel1L deficiency in SCs impaired the ERAD activity of the Sel1L‐Hrd1 complex and led to ER stress and activation of the UPR. Interestingly, Sel1L deficiency had no effect on actively myelinating SCs during development, but led to later‐onset mature SC apoptosis and demyelination in the adult PNS. Moreover, inactivation of the pancreatic ER kinase (PERK) branch of the UPR did not influence the viability and function of actively myelinating SCs, but resulted in exacerbation of ER stress and apoptosis of mature SCs in SC‐specific Sel1L deficient mice. These findings suggest that the integrated UPR and ERAD is dispensable to actively myelinating SCs during development, but is necessary for maintaining ER homeostasis and the viability and function of mature SCs in adults.