Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells

Fikadu Geta Tafesse, Klazien Huitema, Martin Hermansson, Seléne Van Der Poel, Joep Van Den Dikkenberg, Andreas Uphoff, Pentti Somerharju, Joost C.M. Holthuis

Research output: Contribution to journalArticle

145 Scopus citations

Abstract

Sphingomyelin (SM) is a vital component of cellular membranes in organisms ranging from mammals to protozoa. Its production involves the transfer of phosphocholine from phosphatidylcholine to ceramide, yielding diacylglycerol in the process. The mammalian genome encodes two known SM synthase (SMS) isoforms, SMS1 and SMS2. However, the relative contributions of these enzymes to SM production in mammalian cells remained to be established. Here we show that SMS1 and SMS2 are co-expressed in a variety of cell types and function as the key Golgi- and plasma membrane-associated SM synthases in human cervical carcinoma HeLa cells, respectively. RNA interference-mediated depletion of either SMS1 or SMS2 caused a substantial decrease in SM production levels, an accumulation of ceramides, and a block in cell growth. Although SMS-depleted cells displayed a reduced SM content, external addition of SM did not restore growth. These results indicate that the biological role of SM synthases goes beyond formation of SM.

Original languageEnglish (US)
Pages (from-to)17537-17547
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number24
DOIs
StatePublished - Jun 15 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Tafesse, F. G., Huitema, K., Hermansson, M., Van Der Poel, S., Van Den Dikkenberg, J., Uphoff, A., Somerharju, P., & Holthuis, J. C. M. (2007). Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells. Journal of Biological Chemistry, 282(24), 17537-17547. https://doi.org/10.1074/jbc.M702423200