Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis
Open accessAbstract
Multiple sclerosis (MS) is an autoimmune disease in which myelin is progressively degraded. Because degraded myelin may both initiate and accelerate disease progression, clearing degraded myelin from extracellular spaces may be critical. In this study, we prepared myelin vesicles (MV) from rat brains as a model of degraded myelin. Murine embryonic fibroblasts (MEFs) rapidly internalized MVs, which accumulated in lysosomes only when these cells expressed low-density lipoprotein receptor-related protein (LRP1). Receptor-associated protein (RAP), which binds LRP1 and inhibits interaction with other ligands, blocked MV uptake by LRP1-expressing MEFs. As a complementary approach, we prepared primary cultures of rat astrocytes, microglia and oligodendrocytes. All three cell types expressed LRP1 and mediated MV uptake, which was inhibited by RAP. LRP1 gene-silencing in oligodendrocytes also blocked MV uptake. Myelin basic protein (MBP), which was expressed as a recombinant protein, bound directly to LRP1. MBP-specific antibody inhibited MV uptake by oligodendrocytes. In experimental autoimmune encephalomyelitis in mice, LRP1 protein expression was substantially increased in the cerebellum and spinal cord. LRP1 colocalized with multiple CNS cell types. These studies establish LRP1 as a major receptor for phagocytosis of degraded myelin, which may function alone or in concert with co-receptors previously implicated in myelin phagocytosis.
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Lrp1 is highly expressed in astrocytes, where it is responsible for phagocytosis of degraded myelin.
“Lrp1 is highly expressed in astrocytes, where it is responsible for phagocytosis of degraded myelin [78, 79].”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [79]
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“Lrp1 is highly expressed in astrocytes, where it is responsible for phagocytosis of degraded myelin [78, 79].”
BackgroundAuderset, L., Pitman, K. A., Cullen, C. L., Pepper, R. E., Taylor, B. V., Foa, L., & Young, K. M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564351 · Cited by 30 · see citing works
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- Authors
- Gaultier, A., Wu, X., Le Moan, N., Takimoto, S., Mukandala, G., Akassoglou, K., Campana, W. M., & Gonias, S. L.
- Affiliations
- University of California San Diego (US)
- Carolinas Medical Center (US)
- Gladstone Institute of Neurological Diseases, University of California, San Francisco, San Francisco, CA 94158, USA
- University of California, San Francisco (US)
- Corresponding author
- Gonias, Steven L.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2009-04-15
- Volume
- 122
- Issue
- 8
- Pages
- 1155-1162
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC2714439
- OpenAlex
- W2018873526
- Cited by
- 118
- References
- 57
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 8 · 2023: 10 · 2022: 12 · 2021: 8 · 2020: 8 · 2019: 11 · 2018: 6 · 2017: 4 · 2016: 9 · 2015: 7 · 2014: 2 · 2013: 7 · 2012: 6
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cell Science (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health (R01 NS)
- National Heart, Lung, and Blood Institute (R01HL060551, HL60551)
- National Institute of Neurological Disorders and Stroke (NS057456, NS052189, R01NS054671, R01NS052189, R01NS057456)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- LRP1, myelin phagocytosis, receptor-associated protein, myelin basic protein, oligodendrocytes, microglia, astrocytes, lysosomal uptake, experimental autoimmune encephalomyelitis, multiple sclerosis
- MeSH terms
- Animals, Animals, Newborn, Cells, Cultured, Central Nervous System, Cerebellum, Myelin Basic Protein, Encephalomyelitis, Autoimmune, Experimental, Humans, Ligands, Lysosomes, Myelin Sheath, Neuroglia, Phagocytosis, Receptors, LDL, Spinal Cord, Transfection, Rats, Sprague-Dawley, rap GTP-Binding Proteins, Tumor Suppressor Proteins, Low Density Lipoprotein Receptor-Related Protein-1, RNA Interference, RNA, Small Interfering, Mice, Rats
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