Assembly of Myelin by Association of Proteolipid Protein with Cholesterol- and Galactosylceramide-Rich Membrane Domains
Open accessAbstract
Myelin is a specialized membrane enriched in glycosphingolipids and cholesterol that contains a limited spectrum of proteins. We investigated the assembly of myelin components by oligodendrocytes and analyzed the role of lipid–protein interactions in this process. Proteolipid protein (PLP), the major myelin protein, was recovered from cultured oligodendrocytes from a low-density CHAPS-insoluble membrane fraction (CIMF) enriched in myelin lipids. PLP associated with the CIMF after leaving the endoplasmic reticulum but before exiting the Golgi apparatus, suggesting that myelin lipid and protein components assemble in the Golgi complex. The specific association of PLP with myelin lipids in CIMF was supported by the finding that it was efficiently cross-linked to photoactivable cholesterol, but not to phosphatidylcholine, which is underrepresented in both myelin and CIMF. Furthermore, depletion of cholesterol or inhibition of sphingolipid synthesis in oligodendrocytes abolished the association of PLP with CIMF. Thus, PLP may be recruited to myelin rafts, represented by CIMF, via lipid–protein interactions. In contrast to oligodendrocytes, after transfection in BHK cells, PLP is absent from isolated CIMF, suggesting that PLP requires specific lipids for raft association. In mice deficient in the enzyme ceramide galactosyl transferase, which cannot synthesize the main myelin glycosphingolipids, a large fraction of PLP no longer associates with rafts. Formation of a cholesterol- and galactosylceramide-rich membrane domain (myelin rafts) may be critical for the sorting of PLP and assembly of myelin in oligodendrocytes.
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Extra cholesterol supply is key for proper myelin protein assembly and sorting.
“The extra cholesterol supply is not simply the building blocks for lipid content in the myelin sheet, but also the key for proper myelin protein assembly and sorting (Simons et al. 2000).”
From Apolipoprotein E ε4 disrupts oligodendrocyte differentiation by interfering with astrocyte‐derived lipid transport (2023) · cites this paper as Simons et al. 2000
The Results section (“Cholesterol Interacts with PLP/DM20 and Is Required for the Formation of CIMF”; page not provided) reports that cholesterol depletion reduced PLP/DM20 association with a myelin-lipid-rich membrane fraction. The Discussion (page not provided) links that association to sorting during myelin assembly. The paper supports a role for cholesterol in this process, but does not establish that an extra cholesterol supply is needed or test proper assembly and sorting of myelin proteins generally. (LLM, conf=0.85)
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- Authors
- Simons, M., Krämer, E.-M., Thiele, C., Stoffel, W., & Trotter, J.
- Affiliations
- Heidelberg University (DE)
- aDepartment of Neurobiology, University of Heidelberg, 69120 Heidelberg, Germany
- University of Cologne (DE)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2000-10-02
- Volume
- 151
- Issue
- 1
- Pages
- 143-154
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2189802
- OpenAlex
- W2098744846
- Cited by
- 293
- References
- 58
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 12 · 2021: 5 · 2020: 10 · 2019: 15 · 2018: 3 · 2017: 12 · 2016: 4 · 2015: 8 · 2014: 17 · 2013: 9 · 2012: 14
- FWCI
- 5.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
- Keywords
- proteolipid protein, lipid rafts, oligodendrocytes, cholesterol, galactosylceramide, glycosphingolipids, protein-lipid interactions, Golgi apparatus, sphingolipid biosynthesis
- MeSH terms
- Animals, Brain Chemistry, Cell Fractionation, Cholesterol, Cholic Acids, Detergents, Endoplasmic Reticulum, Galactosylceramides, Galactosyltransferases, Golgi Apparatus, Cricetinae, Myelin Sheath, Oligodendroglia, Solubility, Glycosylphosphatidylinositols, Mice, Knockout, Myelin Proteolipid Protein, Hemagglutinin Glycoproteins, Influenza Virus, Membrane Microdomains, N-Acylsphingosine Galactosyltransferase, Mice
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