Identification of a family of animal sphingomyelin synthases
Identification of a family of animal sphingomyelin synthases
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DOI：
10.1038/sj.emboj.7600034
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发表时间：
2004-01-14
期刊：
影响因子：
11.4
通讯作者：
Holthuis, JCM
中科院分区：
文献类型：
--
作者：
Huitema, K;van den Dikkenberg, J;Holthuis, JCM
鞘磷脂（SM）是动物质膜的主要成分。其生产涉及将磷酸胆碱从磷脂酰胆碱转移到神经酰胺上，产生副产物二酰甘油。该反应由 SM 合酶催化，该酶的生物潜力可以通过二酰基甘油和神经酰胺分别作为抗凋亡刺激物和促凋亡刺激物的作用来判断。 SM 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 SM 合酶基因，因此尚不清楚这些位置是否存在不同的酶。利用酵母中的功能性克隆策略，我们鉴定了一个新的整合膜蛋白家族，该家族表现出先前归因于动物 SM 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基因组均包含至少两个不同的 SM 合酶 (SMS) 基因。人类 SMS1 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鞘脂功能开辟了重要的新途径。
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.