Adaptive autophagy reprogramming in Schwann cells during peripheral demyelination

Autor: Young Rae Jo, Yuna Oh, Young Hee Kim, Yoon Kyung Shin, Hye Ran Kim, Hana Go, Jaekyoon Shin, Hye Ji Park, Hyongjong Koh, Jong Kuk Kim, Jung Eun Shin, Kyung Eun Lee, Hwan Tae Park
Rok vydání: 2023
Předmět:
Zdroj: Cellular and Molecular Life Sciences. 80
ISSN: 1420-9071
1420-682X
DOI: 10.1007/s00018-022-04683-7
Popis: The myelin sheath is an essential structure for the rapid transmission of electrical impulses through axons, and peripheral myelination is a well-programmed postnatal process of Schwann cells (SCs), the myelin-forming peripheral glia. SCs transdifferentiate into demyelinating SCs (DSCs) to remove the myelin sheath during Wallerian degeneration after axonal injury and demyelinating neuropathies, and macrophages are responsible for the degradation of myelin under both conditions. In this study, the mechanism by which DSCs acquire the ability of myelin exocytosis was investigated. Using serial ultrastructural evaluation, we found that autophagy-related gene 7-dependent formation of a “secretory phagophore (SP)” and tubular phagophore was necessary for exocytosis of large myelin chambers by DSCs. DSCs seemed to utilize myelin membranes for SP formation and employed p62/sequestosome-1 (p62) as an autophagy receptor for myelin excretion. In addition, the acquisition of the myelin exocytosis ability of DSCs was associated with the decrease in canonical autolysosomal flux and was demonstrated by p62 secretion. Finally, this SC demyelination mechanism appeared to also function in inflammatory demyelinating neuropathies. Our findings show a novel autophagy-mediated myelin clearance mechanism by DSCs in response to nerve damage.
Databáze: OpenAIRE
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