title: Autophagy is involved in the reduction of myelinating Schwann cell cytoplasm during myelin maturation of the peripheral nerve.
abstract: Peripheral nerve myelination involves dynamic changes in Schwann cell morphology and membrane structure. Recent studies have demonstrated that autophagy regulates organelle biogenesis and plasma membrane dynamics. In the present study, we investigated the role of autophagy in the development and differentiation of myelinating Schwann cells during sciatic nerve myelination. Electron microscopy and biochemical assays have shown that Schwann cells remove excess cytoplasmic organelles during myelination through macroautophagy. Inhibition of autophagy via Schwann cell-specific removal of ATG7, an essential molecule for macroautophagy, using a conditional knockout strategy, resulted in abnormally enlarged abaxonal cytoplasm in myelinating Schwann cells that contained a large number of ribosomes and an atypically expanded endoplasmic reticulum. Small fiber hypermyelination and minor anomalous peripheral nerve functions are observed in this mutant. Rapamycin-induced suppression of mTOR activity during the early postnatal period enhanced not only autophagy but also developmental reduction of myelinating Schwann cells cytoplasm in vivo. Together, our findings suggest that autophagy is a regulatory mechanism of Schwann cells structural plasticity during myelination.
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Busan, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Jang
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Busan, Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Pharmacology, Mitochondria Hub Regulation Center, Busan, Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Busan, Korea.
authors.forename: Joo Youn
authors.initials: JY
authors.lastname: Park
authors.affiliation: Department of Pathology, College of Medicine, Dong-A University, Busan, Korea.
authors.forename: Seo-Hee
authors.initials: SH
authors.lastname: Rha
authors.affiliation: Department of Neurology, College of Medicine, Dong-A University, Busan, Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Mitochondria Hub Regulation Center, Busan, Korea.
authors.forename: Hye Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Physiology, Mitochondria Hub Regulation Center, Busan, Korea.
authors.forename: Hwan Tae
authors.initials: HT
authors.lastname: Park
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071193:Autophagy-Related Protein 7; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism / Q000502:physiology*; D012270:Ribosomes / Q000378:metabolism / Q000502:physiology; D012583:Schwann Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D000071193:Autophagy-Related Protein 7