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Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER
Open accessAbstract
Ceramides are central intermediates of sphingolipid metabolism with critical functions in cell organization and survival. They are synthesized on the cytosolic surface of the endoplasmic reticulum (ER) and transported by ceramide transfer protein to the Golgi for conversion to sphingomyelin (SM) by SM synthase SMS1. In this study, we report the identification of an SMS1-related (SMSr) enzyme, which catalyses the synthesis of the SM analogue ceramide phosphoethanolamine (CPE) in the ER lumen. Strikingly, SMSr produces only trace amounts of CPE, i.e., 300-fold less than SMS1-derived SM. Nevertheless, blocking its catalytic activity causes a substantial rise in ER ceramide levels and a structural collapse of the early secretory pathway. We find that the latter phenotype is not caused by depletion of CPE but rather a consequence of ceramide accumulation in the ER. Our results establish SMSr as a key regulator of ceramide homeostasis that seems to operate as a sensor rather than a converter of ceramides in the ER.
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A RAPID METHOD OF TOTAL LIPID EXTRACTION AND PURIFICATION
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Cited by
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Merrill, A. H. (2011) · Chemical Reviews · doi:10.1021/cr2002917 · Cited by 785
Orm family proteins mediate sphingolipid homeostasis
Breslow, D. K., Collins, S. R., Bodenmiller, B., Aebersold, R., Simons, K., Shevchenko, A., Ejsing, C. S., & Weissman, J. S. (2010) · Nature · doi:10.1038/nature08787 · Cited by 599
Biological functions of sphingomyelins
Slotte, J. P. (2013) · Progress in Lipid Research · doi:10.1016/j.plipres.2013.05.001 · Cited by 384
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Fyrst, H., & Saba, J. D. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.392 · Cited by 344
DAG tales: the multiple faces of diacylglycerol—stereochemistry, metabolism, and signaling
Eichmann, T. O., & Lass, A. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1982-3 · Cited by 314
Metadata
- Authors
- Vacaru, A. M., Tafesse, F. G., Ternes, P., Kondylis, V., Hermansson, M., Brouwers, J. F. H. M., Somerharju, P., Rabouille, C., & Holthuis, J. C. M.
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-06-08
- Volume
- 185
- Issue
- 6
- Pages
- 1013-1027
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2037559271
- Cited by
- 168
- References
- 2
- FWCI
- 4.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Vacaru, A. M., Tafesse, F. G., Ternes, P., Kondylis, V., Hermansson, M., Brouwers, J. F. H. M., Somerharju, P., Rabouille, C., & Holthuis, J. C. M. (2009). Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. Journal of Cell Biology. https://doi.org/10.1083/jcb.200903152
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