Journal Article

DZNE-2024-01378

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Nonvesicular lipid transfer drives myelin growth in the central nervous system.

Wu, J. (First author)DZNE* ; Kislinger, G.DZNE* ; Duschek, J.Extern* ; Durmaz, A. D.DZNE* ; Wefers, B.DZNE* ; Feng, R.DZNE* ; Nalbach, K.Extern* ; Wurst, W.DZNE* ; Behrends, C. ; Schifferer, M.DZNE* ; Simons, M. (Last author)DZNE*

2024
Nature Publishing Group UK [London]

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Please use a persistent id in citations: doi:10.1038/s41467-024-53511-y

Abstract: 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.

Keyword(s): Animals (MeSH) ; Myelin Sheath: metabolism (MeSH) ; Oligodendroglia: metabolism (MeSH) ; Oligodendroglia: cytology (MeSH) ; Mice (MeSH) ; Central Nervous System: metabolism (MeSH) ; Central Nervous System: growth & development (MeSH) ; Mice, Knockout (MeSH) ; Endoplasmic Reticulum: metabolism (MeSH) ; Carrier Proteins: metabolism (MeSH) ; Carrier Proteins: genetics (MeSH) ; Lipid Metabolism (MeSH) ; Glycolipids: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Biological Transport (MeSH) ; Carrier Proteins ; Glycolipids ; lipid transfer protein

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Contributing Institute(s):

1. Molecular Neurobiology (AG Simons)
2. Genome Engineering (AG Wurst)
3. Neuronal Cell Biology (AG Misgeld)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

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Database coverage:
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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Wu, J.DZNE*
Dataset: Lipidomics of myelin from wild-type and Gltp cKO mice, v1
Zenodo (2024) [10.5281/zenodo.13779035]2024 BibTeX | EndNote: XML, Text | RIS

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