Cited by 453Autophagy in Disease and TherapyNerve injury and regenerationHereditary Neurological Disorders

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

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Gomez-Sanchez, Jose A., Carty, Lucy, Iruarrizaga-Lejarreta, Marta, Palomo-Irigoyen, Marta, Varela-Rey, Marta, Griffith, Megan, Hantke, Janina, Macias-Camara, Nuria, Azkargorta, Mikel, Aurrekoetxea, Igor, De Juan, Virginia Gutiérrez, Jefferies, Harold B.J., Aspichueta, Patricia, Elortza, Félix, Aransay, Ana M., Martínez-Chantar, María L., Baas, Frank, Mato, José M., Mirsky, Rhona, Woodhoo, Ashwin, Jessen, Kristján R.·2015·Journal of Cell Biology

DOI 10.1083/jcb.201503019PMC PMC4494002

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Abstract

Although Schwann cell myelin breakdown is the universal outcome of a remarkably wide range of conditions that cause disease or injury to peripheral nerves, the cellular and molecular mechanisms that make Schwann cell–mediated myelin digestion possible have not been established. We report that Schwann cells degrade myelin after injury by a novel form of selective autophagy, myelinophagy. Autophagy was up-regulated by myelinating Schwann cells after nerve injury, myelin debris was present in autophagosomes, and pharmacological and genetic inhibition of autophagy impaired myelin clearance. 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.

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Additional file 8 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 6 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 9 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 4 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 7 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 5 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 3 of An RNA-sequencing transcriptome of the rodent Schwann cell response to peripheral nerve injury
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Additional file 5 of Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells
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Additional file 3 of Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells
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Additional file 4 of Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells
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Authors: Gomez-Sanchez, J. A., Carty, L., Iruarrizaga-Lejarreta, M., Palomo-Irigoyen, M., Varela-Rey, M., Griffith, M., Hantke, J., Macias-Camara, N., Azkargorta, M., Aurrekoetxea, I., De Juan, V. G., Jefferies, H. B. J., Aspichueta, P., Elortza, F., Aransay, A. M., Martínez-Chantar, M. L., Baas, F., Mato, J. M., Mirsky, R., Woodhoo, A., & Jessen, K. R.
Affiliations: University College London (GB)
CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain 2
CIC bioGUNE (ES)
Instituto de Salud Carlos III (ES)
University of the Basque Country (ES)
The Francis Crick Institute (GB)
Amsterdam UMC Location University of Amsterdam (NL)
Ikerbasque (ES)
Corresponding author: Woodhoo, Ashwin
ORCID: Gomez-Sanchez, Jose A.
Carty, Lucy
Palomo-Irigoyen, Marta
Azkargorta, Mikel
Aurrekoetxea, Igor
Aspichueta, Patricia
Elortza, Félix
Aransay, Ana M.
Baas, Frank
Mato, José M.
Woodhoo, Ashwin
Jessen, Kristján R.
Venue: Journal of Cell Biology
Publisher: Rockefeller University Press
Published: 2015-07-06
Volume: 210
Issue: 1
Pages: 153-168
ISSN: 0021-9525 (ISSN-L)
1540-8140
DOI: 10.1083/jcb.201503019
PMC: PMC4494002
OpenAlex: W1655540037
Cited by: 453
References: 49
Citations by year: 2026: 33 · 2025: 47 · 2024: 40 · 2023: 45 · 2022: 52 · 2021: 55 · 2020: 43 · 2019: 38 · 2018: 36 · 2017: 32 · 2016: 22 · 2015: 8
FWCI: 25.61
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
Locations: The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Pure Amsterdam UMC (submittedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
UCL Discovery (University College London) (submittedVersion)
Figshare (submittedVersion, cc-by-nc-sa)
Funders: Wellcome Trust (FP7/2007–2013)
Francis Crick Institute (10187)
Cancer Research UK (15153)
Instituto de Salud Carlos III
National Center for Complementary and Integrative Health (R01AT001576)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
Keywords: Schwann cells, selective autophagy, myelin debris clearance, nerve injury, Wallerian degeneration, JNK/c-Jun signaling, demyelinating disease, autophagosomes, myelin debris, central nervous system
MeSH terms: Animals, Autophagy, Cells, Cultured, Mice, Transgenic, Myelin Sheath, Sciatic Nerve, Wallerian Degeneration, Proto-Oncogene Proteins c-jun, JNK Mitogen-Activated Protein Kinases, Lipid Metabolism, TOR Serine-Threonine Kinases, Peripheral Nerve Injuries

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

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