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

Autor:	Gomez-Sanchez JA; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK., Carty L; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK., Iruarrizaga-Lejarreta M; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Palomo-Irigoyen M; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Varela-Rey M; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Griffith M; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK., Hantke J; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK., Macias-Camara N; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Azkargorta M; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain ProteoRed-ISCIII., Aurrekoetxea I; Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain Biocruces Health Research Institute, 48903 Barakaldo, Spain., De Juan VG; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Jefferies HB; The Francis Crick Institute, Lincoln's Inn Fields Laboratory, London WC2A 3LY, England, UK., Aspichueta P; Department of Physiology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain Biocruces Health Research Institute, 48903 Barakaldo, Spain., Elortza F; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain ProteoRed-ISCIII., Aransay AM; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Martínez-Chantar ML; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain Biochemistry and Molecular Biology Department, University of the Basque Country (UPV/EHU), E-48080 Bilbao, Spain., Baas F; Department of Genome Analysis, Academic Medical Centre, 1105 AZ Amsterdam, Netherlands., Mato JM; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain., Mirsky R; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK., Woodhoo A; CIC bioGUNE, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), 48160 Derio, Bizkaia, Spain Ikerbasque, Basque Foundation for Science, 48011 Bilbao, Spain awoodhoo@cicbiogune.es k.jessen@ucl.ac.uk., Jessen KR; Department of Cell and Developmental Biology, University College London, London WC1E 6BT, England, UK awoodhoo@cicbiogune.es k.jessen@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2015 Jul 06; Vol. 210 (1), pp. 153-68.
DOI:	10.1083/jcb.201503019
Abstrakt:	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. (© 2015 Gomez-Sanchez et al.)
Databáze:	MEDLINE
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