Journal article
Modulation of Ceramide Synthase Activity via Dimerization
Journal of Biological Chemistry, Vol.287(25), pp.21025-21033
Jun/2012
Abstract
Ceramide, the backbone of all sphingolipids, is synthesized by a family of ceramide synthases (CerS) that each use acyl-CoAs of defined chain length for N-acylation of the sphingoid long chain base. CerS mRNA expression and enzymatic activity do not always correlate with the sphingolipid acyl chain composition of a particular tissue, suggesting post-translational mechanism(s) of regulation of CerS activity. We now demonstrate that CerS activity can be modulated by dimer formation. Under suitable conditions, high M-r CerS complexes can be detected by Western blotting, and various CerS co-immunoprecipitate. CerS5 activity is inhibited in a dominant-negative fashion by co-expression with catalytically inactive CerS5, and CerS2 activity is enhanced by co-expression with a catalytically active form of CerS5 or CerS6. In a constitutive heterodimer comprising CerS5 and CerS2, the activity of CerS2 depends on the catalytic activity of CerS5. Finally, CerS dimers are formed upon rapid stimulation of ceramide synthesis by curcumin. Together, these data demonstrate that ceramide synthesis can be regulated by the formation of CerS dimers and suggest a novel way to generate the acyl chain composition of ceramide (and downstream sphingolipids), which may depend on the interaction of CerS with each other.
Details
- Title
- Modulation of Ceramide Synthase Activity via Dimerization
- Creators
- Elad L. Laviad (null)Samuel Kelly (null)Alfred H., Jr. Merrill (null)Anthony H. Futerman (null) - 972WIS_INST___112
- Resource Type
- Journal article
- Publication Details
- Journal of Biological Chemistry, Vol.287(25), pp.21025-21033; Jun/2012
- Number of pages
- 9
- Language
- English
- DOI
- https://doi.org/10.1074/jbc.M112.363580
- Grant note
- National Institutes of Health [GM076217]; Israel Science Foundation [1404/07]; Minerva FoundationThis work was supported, in whole or in part, by National Institutes of Health Grant GM076217. This work was also supported by the Israel Science Foundation (1404/07) and the Minerva Foundation._ALMAME_DELIMITER_
- Record Identifier
- 993265502103596
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