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Identification of a Molecular Target of Psychosine and Its Role in Globoid Cell Formation
Open accessAbstract
Globoid cell leukodystrophy (GLD) is characterized histopathologically by apoptosis of oligodendrocytes, progressive demyelination, and the existence of large, multinuclear (globoid) cells derived from perivascular microglia. The glycosphingolipid, psychosine (d-galactosyl-β-1,1′ sphingosine), accumulates to micromolar levels in GLD patients who lack the degradative enzyme galactosyl ceramidase. Here we document that an orphan G protein–coupled receptor, T cell death–associated gene 8, is a specific psychosine receptor. Treatment of cultured cells expressing this receptor with psychosine or structurally related glycosphingolipids results in the formation of globoid, multinuclear cells. Our discovery of a molecular target for psychosine suggests a mechanism for the globoid cell histology characteristic of GLD, provides a tool with which to explore the disjunction of mitosis and cytokinesis in cell cultures, and provides a platform for developing a medicinal chemistry for psychosine.
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Cited by
Le Poul, E., Loison, C., Struyf, S., Springael, J.-Y., Lannoy, V., Decobecq, M.-E., Brezillon, S., Dupriez, V., Vassart, G., Van Damme, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m301403200 · Cited by 1,651
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Hla, T., Lee, M.-J., Ancellin, N., Paik, J. H., & Kluk, M. J. (2001) · Science · doi:10.1126/science.1065323 · Cited by 537
Animal Cytokinesis: From Parts List to Mechanisms
Eggert, U. S., Mitchison, T. J., & Field, C. M. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133425 · Cited by 441
Sphingolipid metabolism diseases
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Metadata
- Authors
- Im, D.-S., Heise, C. E., Nguyen, T., O'Dowd, B. F., & Lynch, K. R.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2001-04-16
- Volume
- 153
- Issue
- 2
- Pages
- 429-434
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2101828749
- Cited by
- 190
- References
- 0
- FWCI
- 10.50
- Type
- journal article
- Language
- en
- Open access
- green
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- Im, D.-S., Heise, C. E., Nguyen, T., O'Dowd, B. F., & Lynch, K. R. (2001). Identification of a Molecular Target of Psychosine and Its Role in Globoid Cell Formation. The Journal of Cell Biology. https://doi.org/10.1083/jcb.153.2.429
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
