TY  - JOUR
AU  - Wu, Jianping
AU  - Kislinger, Georg
AU  - Duschek, Jerome
AU  - Durmaz, Ayşe Damla
AU  - Wefers, Benedikt
AU  - Feng, Ruoqing
AU  - Nalbach, Karsten
AU  - Wurst, Wolfgang
AU  - Behrends, Christian
AU  - Schifferer, Martina
AU  - Simons, Mikael
TI  - Nonvesicular lipid transfer drives myelin growth in the central nervous system.
JO  - Nature Communications
VL  - 15
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2024-01378
SP  - 9756
PY  - 2024
AB  - 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.
KW  - Animals
KW  - Myelin Sheath: metabolism
KW  - Oligodendroglia: metabolism
KW  - Oligodendroglia: cytology
KW  - Mice
KW  - Central Nervous System: metabolism
KW  - Central Nervous System: growth & development
KW  - Mice, Knockout
KW  - Endoplasmic Reticulum: metabolism
KW  - Carrier Proteins: metabolism
KW  - Carrier Proteins: genetics
KW  - Lipid Metabolism
KW  - Glycolipids: metabolism
KW  - Mice, Inbred C57BL
KW  - Biological Transport
KW  - Carrier Proteins (NLM Chemicals)
KW  - Glycolipids (NLM Chemicals)
KW  - lipid transfer protein (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:39528474
C2  - pmc:PMC11554831
DO  - DOI:10.1038/s41467-024-53511-y
UR  - https://pub.dzne.de/record/273899
ER  -