SCAP is required for timely and proper myelin membrane synthesis
Open accessAbstract
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.
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We detect changes in genes associated with myelination and synaptic vesicle endocytosis, including DCX, SCAP, RB1CC1, ADSL and PACSIN1.
“We also detect changes in genes associated with myelination and synaptic vesicle endocytosis, critical to sustain a high rate of synaptic transmission, including DCX104, SCAP105, RB1CC1106, ADSL107 and PACSIN1108 among others (Supplementary Information 2).”
From A catalog of single nucleotide changes distinguishing modern humans from archaic hominins (2019) · cites this paper as [105]
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- Authors
- Verheijen, M. H. G., Camargo, N., Verdier, V., Nadra, K., de Preux Charles, A.-S., Médard, J.-J., Luoma, A., Crowther, M., Inouye, H., Shimano, H., Chen, S., Brouwers, J. F., Helms, J. B., Feltri, M. L., Wrabetz, L., Kirschner, D., Chrast, R., & Smit, A. B.
- Affiliations
- Amsterdam Neuroscience (NL)
- University of Lausanne (CH)
- Department of Medical Genetics, University of Lausanne, CH-1005 Lausanne, Switzerland;
- Boston College (US)
- University of Tsukuba (JP)
- Chainon Neurotrophin Biotechnology Inc., Malta, NY 12020;
- Utrecht University (NL)
- IRCCS Ospedale San Raffaele (IT)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-12-15
- Volume
- 106
- Issue
- 50
- Pages
- 21383-21388
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2795508
- OpenAlex
- W2127234778
- Cited by
- 119
- References
- 33
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 12 · 2015: 4 · 2014: 13 · 2013: 8 · 2012: 8
- FWCI
- 4.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- IRIS (submittedVersion)
- VU Research Portal (submittedVersion)
- SERVAL (Université de Lausanne) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (106714)
- National Institute of Neurological Disorders and Stroke (R01NS045630, R01NS055256)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- SCAP, myelination, Schwann cells, cholesterol biosynthesis, fatty acid synthesis, hypomyelination, lipid metabolism, aging
- MeSH terms
- Aging, Animals, Ganglia, Spinal, Lipids, Membrane Proteins, Mice, Mutant Strains, Mutation, Myelin Sheath, Neuroglia, Schwann Cells, Recovery of Function, Intracellular Signaling Peptides and Proteins, Lipogenesis, Lipid Metabolism, Mice, Sterol Regulatory Element Binding Proteins
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