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  • The EMBO Journal (2004) 23, 33 - 44
  • doi:10.1038/sj.emboj.7600034

Published online: 18 December 2003

Identification of a family of animal sphingomyelin synthases

Klazien Huitema1, Joep van den Dikkenberg1, Jos FHM Brouwers2 and Joost CM Holthuis1

  1. Department of Membrane Enzymology, Faculty of Chemistry, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands
  2. Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands

Correspondence to:

Joost CM Holthuis, Department of Membrane Enzymology, Faculty of Chemistry, University of Utrecht, Padualaan 8, 3584 CH Utrecht, The Netherlands. Tel.: +31 30 253 6630; Fax: +31 30 252 2478; E-mail: j.c.holthuis@chem.uu.nl

Received 1 October 2003; Accepted 20 November 2003

Sphingomyelin (SM) is a major component of animal plasma membranes. Its production involves the transfer of phosphocholine from phosphatidylcholine onto ceramide, yielding diacylglycerol as a side product. This reaction is catalysed by SM synthase, an enzyme whose biological potential can be judged from the roles of diacylglycerol and ceramide as anti- and proapoptotic stimuli, respectively. SM synthesis occurs in the lumen of the Golgi as well as on the cell surface. As no gene for SM synthase has been cloned so far, it is unclear whether different enzymes are present at these locations. Using a functional cloning strategy in yeast, we identified a novel family of integral membrane proteins exhibiting all enzymatic features previously attributed to animal SM synthase. Strikingly, human, mouse and Caenorhabditis elegans genomes each contain at least two different SM synthase (SMS) genes. Whereas human SMS1 is localised to the Golgi, SMS2 resides primarily at the plasma membrane. Collectively, these findings open up important new avenues for studying sphingolipid function in animals.

  • Keywords:

    • apoptosis,
    • ceramide,
    • Golgi,
    • lipid phosphate phosphatase,
    • sphingomyelin synthase