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Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury
Open accessAbstract
Significance: Myelin is a potent inhibitor of axon regeneration. In the central nervous system, failure to clear myelin debris after injury presents a major roadblock to recovery. In contrast, rapid myelin clearance in the peripheral nervous system (PNS) contributes to this system’s remarkable regenerative capacity, but the mechanisms involved have remained incompletely understood. In this work, we set out to identify novel mechanisms of PNS myelin clearance to generate new ideas about activating myelin clearance in the injured CNS. We provide evidence that Schwann cells, myelinating glia of the PNS, engulf myelin debris using two receptors, Axl and Mertk. We hypothesize that astrocytes have the potential to use this same mechanism to engulf myelin debris after CNS injury.
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“After nerve injury, Schwann cells oversee the capture of myelin debris in autophagosomes in a process termed “myelinophagy” [459,462,463],”
From Autophagy and ALS: mechanistic insights and therapeutic implications (2022) · cites this paper as [462]
Citations
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971
Self-citationGuidelines for the use and interpretation of assays for monitoring autophagy
Klionsky, D. J., Abdalla, F. C., Abeliovich, H., Abraham, R. T., Acevedo-Arozena, A., Adeli, K., Agholme, L., Agnello, M., Agostinis, P., Aguirre-Ghiso, J. A., et al. (2012) · Autophagy · doi:10.4161/auto.19496 · Cited by 3,996 · cited 1×
“Lipidation of cytosolic mammalian myosin light chain 3 (LC3) to become LC3-phosphatidylethanolamine (LC3-PE) results in transient association of this protein with nascent autophagosomes and is critical for autophagosome formation (18).”
Complement and microglia mediate early synapse loss in Alzheimer mouse models
Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., et al. (2016) · Science · doi:10.1126/science.aad8373 · Cited by 3,343
Self-citationCahoy, J. D., Emery, B., Kaushal, A., Foo, L. C., Zamanian, J. L., Christopherson, K. S., Xing, Y., Lubischer, J. L., Krieg, P. A., Krupenko, S. A., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4178-07.2008 · Cited by 3,129
Self-citationGenomic analysis of reactive astrogliosis
Zamanian, J. L., Xu, L., Foo, L. C., Nouri, N., Zhou, L., Giffard, R. G., & Barres, B. A. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6221-11.2012 · Cited by 2,404
Self-citationImpairment of starvation-induced and constitutive autophagy in Atg7 -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331
Regulation of Mammalian Autophagy in Physiology and Pathophysiology
Ravikumar, B., Sarkar, S., Davies, J. E., Futter, M., García-Arencibia, M., Green-Thompson, Z. W., Jiménez-Sánchez, M., Korolchuk, V. I., Lichtenberg, M., Luo, S., et al. (2010) · Physiological Reviews · doi:10.1152/physrev.00030.2009 · Cited by 1,789
van Rooijen, N., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,763
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377 · cited 3×
“Recent work from our laboratory, however, has shown that mouse astrocytes express phagocytic pathways and that they phagocytose synaptic debris in the developing and adult brain using Mertk, Megf10, and LRP1 and robustly phagocytose myelin debris in vitro (25, 37).”
BackgroundSelf-citationPhagocytosis of apoptotic cells in homeostasis
Arandjelovic, S., & Ravichandran, K. S. (2015) · Nature Immunology · doi:10.1038/ni.3253 · Cited by 959
Imaging of neutral lipids by oil red O for analyzing the metabolic status in health and disease
Mehlem, A., Hagberg, C. E., Muhl, L., Eriksson, U., & Falkevall, A. (2013) · Nature Protocols · doi:10.1038/nprot.2013.055 · Cited by 917
Wallerian degeneration: gaining perspective on inflammatory events after peripheral nerve injury
Gaudet, A. D., Popovich, P. G., & Ramer, M. S. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-110 · Cited by 903
Arthur‐Farraj, P., Latouche, M., Wilton, D. K., Quintes, S., Chabrol, E., Banerjee, A., Woodhoo, A., Jenkins, B., Rahman, M., Turmaine, M., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.021 · Cited by 866
Schwab, M. E. (2004) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2004.01.004 · Cited by 613
Age-related myelin degradation burdens the clearance function of microglia during aging
Safaiyan, S., Kannaiyan, N., Snaidero, N., Brioschi, S., Biber, K., Yona, S., Edinger, A. L., Jung, S., Rossner, M. J., & Simons, M. (2016) · Nature Neuroscience · doi:10.1038/nn.4325 · Cited by 604
Lemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598
Clearance of apoptotic cells: implications in health and disease
Elliott, M. R., & Ravichandran, K. S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201004096 · Cited by 568
Why is Wallerian degeneration in the CNS so slow?
Vargas, M. E., & Barres, B. A. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094354 · Cited by 510
Self-citationSchwann cell autophagy, myelinophagy, initiates myelin clearance from injured nerves
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., et al. (2015) · Journal of Cell Biology · doi:10.1083/jcb.201503019 · Cited by 453
Napoli, I., Noon, L. A., Ribeiro, S., Kerai, A., Parrinello, S., Rosenberg, L. H., Collins, M. J., Harrisingh, M. C., White, I. J., Woodhoo, A., et al. (2012) · Neuron · doi:10.1016/j.neuron.2011.11.031 · Cited by 409
LYSOSOMES IN THE RAT SCIATIC NERVE FOLLOWING CRUSH
Holtzman, E., & Novikoff, A. B. (1965) · The Journal of Cell Biology · doi:10.1083/jcb.27.3.651 · Cited by 323
Accelerating axonal growth promotes motor recovery after peripheral nerve injury in mice
Ma, C. H. E., Omura, T., Cobos, E. J., Latrémolière, A., Ghasemlou, N., Brenner, G. J., van Veen, J. E., Barrett, L. B., Sawada, T., Gao, F., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58675 · Cited by 263
Contrasting the Glial Response to Axon Injury in the Central and Peripheral Nervous Systems
Lutz, A. B., & Barres, B. A. (2014) · Developmental Cell · doi:10.1016/j.devcel.2013.12.002 · Cited by 233
Self-citationReichert, F., Saada, A., & Rotshenker, S. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-05-03231.1994 · Cited by 230
Draper-dependent glial phagocytic activity is mediated by Src and Syk family kinase signalling
Ziegenfuss, J. S., Biswas, R., Avery, M. A., Hong, K., Sheehan, A. E., Yeung, Y.-G., Stanley, E. R., & Freeman, M. R. (2008) · Nature · doi:10.1038/nature06901 · Cited by 202
Vargas, M. E., Watanabe, J., Singh, S. J., Robinson, W. H., & Barres, B. A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001948107 · Cited by 168
Self-citationBurstyn-Cohen, T., Lew, E. D., Través, P. G., Burrola, P. G., Hash, J. C., & Lemke, G. (2012) · Neuron · doi:10.1016/j.neuron.2012.10.015 · Cited by 163
Jang, S. Y., Shin, Y. K., Park, S., Park, J. Y., Lee, H., Yoo, Y. H., Kim, J. K., & Park, H. T. (2015) · Glia · doi:10.1002/glia.22957 · Cited by 148
Liu, H. M., YANG, L. H., & YANG, Y. J. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199507000-00002 · Cited by 142
Dailey, A. T., Avellino, A. M., Benthem, L., Silver, J., & Kliot, M. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-17-06713.1998 · Cited by 140
Perry, V. H., Tsao, J. W., Feam, S., & Brown, M. C. (1995) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1995.tb01063.x · Cited by 126
Electron Microscopy of the Mouse Central Nervous System
Möbius, W., Cooper, B. H., Kaufmann, W. A., Imig, C., Ruhwedel, T., Snaidero, N., Saab, A. S., & Varoqueaux, F. (2010) · Methods in cell biology · doi:10.1016/s0091-679x(10)96020-2 · Cited by 116
Autophagosomes in GFP-LC3 Transgenic Mice
Mizushima, N., & Kuma, A. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-157-4_7 · Cited by 101
Further Studies on Motor and Sensory Nerve Regeneration in Mice With Delayed Wallerian Degeneration
Brown, M. C., Perry, V. H., Hunt, S. P., & Lapper, S. R. (1994) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1994.tb00285.x · Cited by 100
Peleshok, J. C., & Ribeiro‐da‐Silva, A. (2012) · Molecular Pain · doi:10.1186/1744-8069-8-1 · Cited by 81
Romanelli, E., Merkler, D., Mężydło, A., Weil, M., Weber, M. S., Nikić, I., Potz, S., Meinl, E., Matznick, F. E. H., Kreutzfeldt, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms13275 · Cited by 75
Perineurial Glia Are Essential for Motor Axon Regrowth following Nerve Injury
Lewis, G. M., & Kucenas, S. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1906-14.2014 · Cited by 68
The neurilemma cell in peripheral nerve degeneration and regeneration
Satinsky, D., Pepe, F. A., & Liu, C. N. (1964) · Experimental Neurology · doi:10.1016/0014-4886(64)90052-4 · Cited by 62
Purification of Schwann Cells from the Neonatal and Injured Adult Mouse Peripheral NervePreprint
Lutz, A. B. (2014) · Cold Spring Harbor Protocols · doi:10.1101/pdb.prot074989 · Cited by 13
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Metadata
- Authors
- Brosius Lutz, A., Chung, W.-S., Sloan, S. A., Carson, G. A., Zhou, L., Lovelett, E., Posada, S., Zuchero, J. B., & Barres, B. A.
- Affiliations
- Department of Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305-5125;
- Korea Advanced Institute of Science and Technology (KR)
- Stanford Medicine (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-09-05
- Volume
- 114
- Issue
- 38
- Pages
- E8072-E8080
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5617301
- OpenAlex
- W2752650605
- Cited by
- 225
- References
- 41
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 23 · 2023: 27 · 2022: 30 · 2021: 35 · 2020: 29 · 2019: 22 · 2018: 19
- FWCI
- 9.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (none)
- Christopher and Dana Reeve Foundation (none)
- HHS | National Institutes of Health (EY11310, NIH NS069375, NIH 1S10RR02678001, NIH S10 Shared Instrument Grant S10RR027431-01)
- Stanford Medical Scientist Training Program (none)
- Developmental and Neonatal Biology Training Program (NIH T32 HD007249)
- National Multiple Sclerosis Society (none)
- National Research Foundation of Korea (NRF-2016M3C7A1905391, NRF-2016R1C1B3006969)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- Schwann cells, myelin debris clearance, TAM receptors, AXL, MERTK, phagocytosis, autophagy, peripheral nerve injury, nerve crush injury, macrophages, central nervous system regeneration, astrocytes, myelin debris
- MeSH terms
- c-Mer Tyrosine Kinase, Axl Receptor Tyrosine Kinase, Animals, Autophagy, Disease Models, Animal, Myelin Sheath, Phagocytosis, Proto-Oncogene Proteins, Receptor Protein-Tyrosine Kinases, Mice, Peripheral Nerve Injuries
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