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@ARTICLE{Wu:273899,
author = {Wu, Jianping and Kislinger, Georg and Duschek, Jerome and
Durmaz, Ayşe Damla and Wefers, Benedikt and Feng, Ruoqing
and Nalbach, Karsten and Wurst, Wolfgang and Behrends,
Christian and Schifferer, Martina and Simons, Mikael},
title = {{N}onvesicular lipid transfer drives myelin growth in the
central nervous system.},
journal = {Nature Communications},
volume = {15},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2024-01378},
pages = {9756},
year = {2024},
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.},
keywords = {Animals / Myelin Sheath: metabolism / Oligodendroglia:
metabolism / Oligodendroglia: cytology / Mice / Central
Nervous System: metabolism / Central Nervous System: growth
$\&$ development / Mice, Knockout / Endoplasmic Reticulum:
metabolism / Carrier Proteins: metabolism / Carrier
Proteins: genetics / Lipid Metabolism / Glycolipids:
metabolism / Mice, Inbred C57BL / Biological Transport /
Carrier Proteins (NLM Chemicals) / Glycolipids (NLM
Chemicals) / lipid transfer protein (NLM Chemicals)},
cin = {AG Simons / AG Wurst / AG Misgeld},
ddc = {500},
cid = {I:(DE-2719)1110008 / I:(DE-2719)1140001 /
I:(DE-2719)1110000-4},
pnm = {351 - Brain Function (POF4-351) / 352 - Disease Mechanisms
(POF4-352)},
pid = {G:(DE-HGF)POF4-351 / G:(DE-HGF)POF4-352},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39528474},
pmc = {pmc:PMC11554831},
doi = {10.1038/s41467-024-53511-y},
url = {https://pub.dzne.de/record/273899},
}