Jo, Young Rae 오유나 Kim, Young Hee Shin, Yoon Kyung Kim, Hye Ran Go, Hana Shin, Jaekyoon Park, Hye Ji Koh, Hyongjong Kim, Jong Kuk Shin, Jung Eun Lee, Kyung Eun Park, Hwan Tae 2024-01-19T10:30:53Z 2024-01-19T10:30:53Z 2023-02-03 2023-01 1420-682X https://pubs.kist.re.kr/handle/201004/114139 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. English Birkhauser Verlag Adaptive autophagy reprogramming in Schwann cells during peripheral demyelination Article 10.1007/s00018-022-04683-7 1 Cellular and Molecular Life Sciences, v.80, no.1 Cellular and Molecular Life Sciences 80 1 N scie scopus 000911481100001 2-s2.0-85145910581 Biochemistry & Molecular Biology Cell Biology Biochemistry & Molecular Biology Cell Biology Article LYSOSOMAL EXOCYTOSIS MYELIN CLEARANCE REGENERATION SECRETION MECHANISM REPORTER Autophagy Demyelination Demyelinating neuropathy SQSTM1 p62 Wallerian degeneration