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000273899 1001_ $$0P:(DE-2719)9000820$$aWu, Jianping$$b0$$eFirst author
000273899 245__ $$aNonvesicular lipid transfer drives myelin growth in the central nervous system.
000273899 260__ $$a[London]$$bNature Publishing Group UK$$c2024
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000273899 520__ $$aOligodendrocytes extend numerous cellular processes that wrap multiple times around axons to generate lipid-rich myelin sheaths. Myelin biogenesis requires an enormously productive biosynthetic machinery for generating and delivering these large amounts of newly synthesized lipids. Yet, a complete understanding of this process remains elusive. Utilizing volume electron microscopy, we demonstrate that the oligodendroglial endoplasmic reticulum (ER) is enriched in developing myelin, extending into and making contact with the innermost myelin layer where growth occurs. We explore the possibility of transfer of lipids from the ER to myelin, and find that the glycolipid transfer protein (GLTP), implicated in nonvesicular lipid transport, is highly enriched in the growing myelin sheath. Mice with a specific knockout of Gltp in oligodendrocytes exhibit ER pathology, hypomyelination and a decrease in myelin glycolipid content. In summary, our results demonstrate a role for nonvesicular lipid transport in CNS myelin growth, revealing a cellular pathway in developmental myelination.
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000273899 650_7 $$2NLM Chemicals$$aCarrier Proteins
000273899 650_7 $$2NLM Chemicals$$aGlycolipids
000273899 650_7 $$2NLM Chemicals$$alipid transfer protein
000273899 650_2 $$2MeSH$$aAnimals
000273899 650_2 $$2MeSH$$aMyelin Sheath: metabolism
000273899 650_2 $$2MeSH$$aOligodendroglia: metabolism
000273899 650_2 $$2MeSH$$aOligodendroglia: cytology
000273899 650_2 $$2MeSH$$aMice
000273899 650_2 $$2MeSH$$aCentral Nervous System: metabolism
000273899 650_2 $$2MeSH$$aCentral Nervous System: growth & development
000273899 650_2 $$2MeSH$$aMice, Knockout
000273899 650_2 $$2MeSH$$aEndoplasmic Reticulum: metabolism
000273899 650_2 $$2MeSH$$aCarrier Proteins: metabolism
000273899 650_2 $$2MeSH$$aCarrier Proteins: genetics
000273899 650_2 $$2MeSH$$aLipid Metabolism
000273899 650_2 $$2MeSH$$aGlycolipids: metabolism
000273899 650_2 $$2MeSH$$aMice, Inbred C57BL
000273899 650_2 $$2MeSH$$aBiological Transport
000273899 7001_ $$0P:(DE-2719)9000614$$aKislinger, Georg$$b1
000273899 7001_ $$0P:(DE-2719)9003122$$aDuschek, Jerome$$b2$$udzne
000273899 7001_ $$0P:(DE-2719)9002505$$aDurmaz, Ayşe Damla$$b3$$udzne
000273899 7001_ $$0P:(DE-2719)2810988$$aWefers, Benedikt$$b4
000273899 7001_ $$0P:(DE-2719)9002625$$aFeng, Ruoqing$$b5$$udzne
000273899 7001_ $$0P:(DE-2719)9002811$$aNalbach, Karsten$$b6$$udzne
000273899 7001_ $$0P:(DE-2719)2000028$$aWurst, Wolfgang$$b7
000273899 7001_ $$00000-0002-9184-7607$$aBehrends, Christian$$b8
000273899 7001_ $$0P:(DE-2719)2812260$$aSchifferer, Martina$$b9
000273899 7001_ $$0P:(DE-2719)2811642$$aSimons, Mikael$$b10$$eLast author$$udzne
000273899 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-53511-y$$gVol. 15, no. 1, p. 9756$$n1$$p9756$$tNature Communications$$v15$$x2041-1723$$y2024
000273899 7870_ $$0DZNE-2024-01349$$aWu, Jianping$$dZenodo, 2024$$iRelatedTo$$r$$tDataset: Lipidomics of myelin from wild-type and Gltp cKO mice, v1
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