Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells.
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.
Tafesse
Fikadu Geta
FG
Department of Membrane Enzymology, Bijvoet Center and Institute of Biomembranes, Utrecht University, 3584 CH Utrecht, The Netherlands.
Huitema
Klazien
K
Hermansson
Martin
M
van der Poel
Seléne
S
van den Dikkenberg
Joep
J
Uphoff
Andreas
A
Somerharju
Pentti
P
Holthuis
Joost C M
JC
D000818:Animals; D006367:HeLa Cells; D006706:Homeostasis; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D013109:Sphingomyelins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism*
D007527:Isoenzymes; D008055:Lipids; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D013109:Sphingomyelins; C455440:SGMS1 protein, human; D017855:Transferases (Other Substituted Phosphate Groups)