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Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.

Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M, Griffith M, Hantke J, Macias-Camara N, Azkargorta M, Aurrekoetxea I, De Juan VG, Jefferies HB, Aspichueta P, Elortza F, Aransay AM, Martínez-Chantar ML, Baas F, Mato JM, Mirsky R, Woodhoo A, Jessen KR - J. Cell Biol. (2015)

Bottom Line: Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury.We also present evidence that myelinophagy is defective in the injured central nervous system.These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.

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Schwann cell autophagosomes enclose degraded myelin. Electron micrographs show the presence of structures typical of autophagosomes surrounding myelin debris. (A) Myelin debris (M) are surrounded by the double membrane of an autophagosome (arrowheads) within a Schwann cell in a nerve piece. Note the basal lamina surrounding the Schwann cell processes (arrow) and the collagen fibrils outside the basal lamina. (B) Myelin debris (M) and cytoplasm (C) are enclosed by an autophagosome (arrowhead) in a cultured Schwann cell. The myelin is shown at high magnification in the inset.
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fig2: Schwann cell autophagosomes enclose degraded myelin. Electron micrographs show the presence of structures typical of autophagosomes surrounding myelin debris. (A) Myelin debris (M) are surrounded by the double membrane of an autophagosome (arrowheads) within a Schwann cell in a nerve piece. Note the basal lamina surrounding the Schwann cell processes (arrow) and the collagen fibrils outside the basal lamina. (B) Myelin debris (M) and cytoplasm (C) are enclosed by an autophagosome (arrowhead) in a cultured Schwann cell. The myelin is shown at high magnification in the inset.

Mentions: To confirm that the Schwann cell autophagy machinery is selectively targeted to myelin during active digestion, electron microscopy of cultured nerve segments and Schwann cell cultures were performed. We found myelin debris clearly enclosed in double membrane vesicles typical of autophagosomes (Fig. 2). These observations show that autophagy is activated during Wallerian degeneration, specifically in demyelinating Schwann cells.


Schwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves.

Gomez-Sanchez JA, Carty L, Iruarrizaga-Lejarreta M, Palomo-Irigoyen M, Varela-Rey M, Griffith M, Hantke J, Macias-Camara N, Azkargorta M, Aurrekoetxea I, De Juan VG, Jefferies HB, Aspichueta P, Elortza F, Aransay AM, Martínez-Chantar ML, Baas F, Mato JM, Mirsky R, Woodhoo A, Jessen KR - J. Cell Biol. (2015)

Schwann cell autophagosomes enclose degraded myelin. Electron micrographs show the presence of structures typical of autophagosomes surrounding myelin debris. (A) Myelin debris (M) are surrounded by the double membrane of an autophagosome (arrowheads) within a Schwann cell in a nerve piece. Note the basal lamina surrounding the Schwann cell processes (arrow) and the collagen fibrils outside the basal lamina. (B) Myelin debris (M) and cytoplasm (C) are enclosed by an autophagosome (arrowhead) in a cultured Schwann cell. The myelin is shown at high magnification in the inset.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4494002&req=5

fig2: Schwann cell autophagosomes enclose degraded myelin. Electron micrographs show the presence of structures typical of autophagosomes surrounding myelin debris. (A) Myelin debris (M) are surrounded by the double membrane of an autophagosome (arrowheads) within a Schwann cell in a nerve piece. Note the basal lamina surrounding the Schwann cell processes (arrow) and the collagen fibrils outside the basal lamina. (B) Myelin debris (M) and cytoplasm (C) are enclosed by an autophagosome (arrowhead) in a cultured Schwann cell. The myelin is shown at high magnification in the inset.
Mentions: To confirm that the Schwann cell autophagy machinery is selectively targeted to myelin during active digestion, electron microscopy of cultured nerve segments and Schwann cell cultures were performed. We found myelin debris clearly enclosed in double membrane vesicles typical of autophagosomes (Fig. 2). These observations show that autophagy is activated during Wallerian degeneration, specifically in demyelinating Schwann cells.

Bottom Line: Myelinophagy was positively regulated by the Schwann cell JNK/c-Jun pathway, a central regulator of the Schwann cell reprogramming induced by nerve injury.We also present evidence that myelinophagy is defective in the injured central nervous system.These results reveal an important role for inductive autophagy during Wallerian degeneration, and point to potential mechanistic targets for accelerating myelin clearance and improving demyelinating disease.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK.

Show MeSH
Related in: MedlinePlus