Palmitoylation is a sorting determinant for transport to the myelin membrane
2005 | journal article. A publication with affiliation to the University of Göttingen.
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Palmitoylation is a sorting determinant for transport to the myelin membrane
Schneider, A.; Lander, H.; Schulz, G.; Wolburg, H.; Nave, K. A.; Schulz, J. B. & Simons, M. (2005)
Journal of Cell Science, 118(11) pp. 2415-2423. DOI: https://doi.org/10.1242/jcs.02365
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- Authors
- Schneider, Anja; Lander, H.; Schulz, G.; Wolburg, Hartwig; Nave, K. A.; Schulz, Joerg B.; Simons, Mikael
- Abstract
- Myelin is a specialized membrane enriched in glycosphingolipids and cholesterol that contains a restricted set of proteins. The mechanisms by which oligodendrocytes target myelin components to myelin are not known. To identify the sorting determinants for protein transport to myelin, we used a primary oligodendrocyte culture system in which terminal differentiation is synchronized and there is excessive deposition of myelin-like membranes (MLMs). Because several myelin proteins are palmitoylated, we explored the role of acylation in protein transport to MLMs. We found that palmitoylation-deficient mutants of a major myelin protein, proteolipid protein (PLP/DM20), were less efficiently targeted to MLMs. The N-terminal 13 amino acids of PLP/DM20, which are palmitoylated at three sites, were sufficient to direct a fluorescent fusion protein to MLMs. Mutagenesis of the N-terminal palmitoylation motif abolished the transport of the fusion protein to MLMs, indicating that palmitoylation is required for sorting to myelin. Similar results were obtained in myelinating co-cultures of oligodendrocytes and neurons. Furthermore, the combined farnesylation/palmitoylation signals from c-Ha-Ras and the N-terminal consensus sequence for dual palmitoylation from neuromodulin were sufficient for the transport of fluorescent fusion proteins to MLMs. Thus, we conclude that palmitoylation is a sorting determinant for transport to the myelin membrane.
- Issue Date
- 2005
- Status
- published
- Publisher
- Company Of Biologists Ltd
- Journal
- Journal of Cell Science
- ISSN
- 0021-9533