SCAP is required for timely and proper myelin membrane synthesis.

Détails

ID Serval
serval:BIB_2F1A5649797D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
SCAP is required for timely and proper myelin membrane synthesis.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur⸱e⸱s
Verheijen Mark H. G., Camargo Nutabi, Verdier Valerie, Nadra Karim, Charles Anne-Sophie de Preux, Medard Jean-Jacques, Luoma Adrienne, Crowther Michelle, Inouye Hideyo, Shimano Hitoshi, Chen Su, Brouwers Jos F., Helms J. Bernd , Feltri M. Laura , Wrabetz Lawrence, Kirschner Daniel, Chrast Roman, Smit August. B. 
ISSN
1091-6490[electronic]
Statut éditorial
Publié
Date de publication
2009
Volume
106
Numéro
50
Pages
21383-21388
Langue
anglais
Résumé
Myelination requires a massive increase in glial cell membrane synthesis. Here, we demonstrate that the acute phase of myelin lipid synthesis is regulated by sterol regulatory element-binding protein (SREBP) cleavage activation protein (SCAP), an activator of SREBPs. Deletion of SCAP in Schwann cells led to a loss of SREBP-mediated gene expression involving cholesterol and fatty acid synthesis. Schwann cell SCAP mutant mice show congenital hypomyelination and abnormal gait. Interestingly, aging SCAP mutant mice showed partial regain of function; they exhibited improved gait and produced small amounts of myelin indicating a slow SCAP-independent uptake of external lipids. Accordingly, extracellular lipoproteins partially rescued myelination by SCAP mutant Schwann cells. However, SCAP mutant myelin never reached normal thickness and had biophysical abnormalities concordant with abnormal lipid composition. These data demonstrate that SCAP-mediated regulation of glial lipogenesis is key to the proper synthesis of myelin membrane, and provide insight into abnormal Schwann cell function under conditions affecting lipid metabolism.
Mots-clé
Lipid Metabolism, Neuron-Glia Interactions, Neuropathy, X-Ray Diffraction, Peripheral Nervous-System, Schwann-Cells, Transgenic Mice, Fatty-Acids, Cholesterol, Galactocerebroside, Bilayers, Growth, Level
Pubmed
Web of science
Open Access
Oui
Création de la notice
06/01/2010 8:53
Dernière modification de la notice
20/08/2019 13:13
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