Nonvesicular lipid transfer drives myelin growth in the central nervous system

Oligodendrocytes extend numerous cellular processes that wrap multiple times around axons to generate lipid-rich myelin sheaths. Myelin biogenesis requires an enormously productive biosynthetic machinery for generating and delivering these large amounts of newly synthesized lipids. Yet, a complete u...

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Bibliographic Details
Published in:	Nature communications Vol. 15; no. 1; pp. 9756 - 15
Main Authors:	Wu, Jianping, Kislinger, Georg, Duschek, Jerome, Durmaz, Ayşe Damla, Wefers, Benedikt, Feng, Ruoqing, Nalbach, Karsten, Wurst, Wolfgang, Behrends, Christian, Schifferer, Martina, Simons, Mikael
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 11-11-2024 Nature Publishing Group Nature Portfolio
Subjects:	13 13/51 631/378/2596/1705 631/378/87 64 64/110 64/60 82/80 Axonogenesis Axons Central nervous system Electron microscopy Endoplasmic reticulum Humanities and Social Sciences Lipids multidisciplinary Myelin Myelination Oligodendrocytes Protein transport Science Science (multidisciplinary) Sheaths
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Summary:	Oligodendrocytes extend numerous cellular processes that wrap multiple times around axons to generate lipid-rich myelin sheaths. Myelin biogenesis requires an enormously productive biosynthetic machinery for generating and delivering these large amounts of newly synthesized lipids. Yet, a complete understanding of this process remains elusive. Utilizing volume electron microscopy, we demonstrate that the oligodendroglial endoplasmic reticulum (ER) is enriched in developing myelin, extending into and making contact with the innermost myelin layer where growth occurs. We explore the possibility of transfer of lipids from the ER to myelin, and find that the glycolipid transfer protein (GLTP), implicated in nonvesicular lipid transport, is highly enriched in the growing myelin sheath. Mice with a specific knockout of Gltp in oligodendrocytes exhibit ER pathology, hypomyelination and a decrease in myelin glycolipid content. In summary, our results demonstrate a role for nonvesicular lipid transport in CNS myelin growth, revealing a cellular pathway in developmental myelination. To generate myelin, oligodendrocytes must greatly expand their membrane. Here, the authors show that oligodendroglial endoplasmic reticulum-myelin contact sites and nonvesicular glycolipid transport are involved in this process.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-024-53511-y