Huitema Klazien, van den Dikkenberg Joep, Brouwers Jos F H M, Holthuis Joost C M
Department of Membrane Enzymology, Faculty of Chemistry, Institute of Biomembranes, Utrecht University, Utrecht, The Netherlands.
EMBO J. 2004 Jan 14;23(1):33-44. doi: 10.1038/sj.emboj.7600034. Epub 2003 Dec 18.
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.
鞘磷脂（SM）是动物质膜的主要成分。其产生涉及磷酸胆碱从磷脂酰胆碱转移到神经酰胺上，产生二酰基甘油作为副产物。该反应由鞘磷脂合酶催化，从二酰基甘油和神经酰胺分别作为抗凋亡和促凋亡刺激物的作用可以判断该酶的生物学潜能。鞘磷脂合成发生在高尔基体腔以及细胞表面。由于迄今为止尚未克隆出鞘磷脂合酶基因，目前尚不清楚这些位置是否存在不同的酶。我们利用酵母中的功能克隆策略，鉴定出一个新的整合膜蛋白家族，该家族展现出先前归因于动物鞘磷脂合酶的所有酶学特征。引人注目的是，人类、小鼠和秀丽隐杆线虫的基因组各自至少包含两个不同的鞘磷脂合酶（SMS）基因。人类SMS1定位于高尔基体，而SMS2主要位于质膜。总的来说，这些发现为研究动物中鞘脂的功能开辟了重要的新途径。
