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Wu, J.* ; Kislinger, G.* ; Duschek, J.* ; Durmaz, A.D.* ; Wefers, B.* ; Feng, R.* ; Nalbach, K.* ; Wurst, W. ; Behrends, C.* ; Schifferer, M.* ; Simons, M.*

Nonvesicular lipid transfer drives myelin growth in the central nervous system.

Nat. Commun. 15:9756 (2024)
Postprint DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Endoplasmic-reticulum; Sheath Formation; Contact Sites; Nogo-a; Membrane; Protein; Oligodendrocyte; Platform; Galactocerebroside; Neurons
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 15, Heft: 1, Seiten: , Artikelnummer: 9756 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Developmental Genetics (IDG)
POF Topic(s) 30204 - Cell Programming and Repair
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-500500-001
Förderungen EU Horizon ERC Advanced Grant
German Research Foundation
Human Frontier Science Program (HFSP)
ERC
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
Chan-Zuckerberg Initiative grant
DOI 10.1038/s41467-024-53511-y
WOS ID 001357982900023
Scopus ID 85209483510
PubMed ID 39528474
Erfassungsdatum 2024-11-19
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