Serinc, an activity-regulated protein family, incorporates serine into membrane lipid synthesis
Serinc, an activity-regulated protein family, incorporates serine into membrane lipid synthesis
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DOI：
10.1074/jbc.m505712200
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发表时间：
2005-10-21
影响因子：
4.8
通讯作者：
Ingi, T
中科院分区：
文献类型：
--
作者：
Inuzuka, M;Hayakawa, M;Ingi, T
细胞膜含有各种转运蛋白，其中一些负责跨膜传递氨基酸。在这项研究中，我们报道了另一类被称为Serinc1 - 5的载体蛋白，它将一个极性氨基酸丝氨酸结合到膜中，并促进两种丝氨酸衍生的脂质的合成，磷脂酰丝氨酸和鞘脂。丝氨酸是一个独特的蛋白质家族，与其他蛋白质没有氨基酸同源性，但在真核生物中高度保守。成员包含11个跨膜结构域，大鼠Serinc1蛋白与内质网膜上的脂质生物合成酶共定位。丝氨酸蛋白与参与丝氨酸和鞘脂生物合成的关键酶形成细胞内复合物，丝氨酸合成和膜结合这两种功能相互联系。在大鼠脑中，海碱盐诱导的海马神经元细胞层中Serinc1和Serinc2 mRNA的表达迅速上调。相反，整个大脑的髓磷脂富含Serinc5，海马中Serinc5因癫痫发作而下调。这些结果表明了神经活动与脂质生物合成之间的新机制。
Cell membranes contain various transporter proteins, some of which are responsible for transferring amino acids across membrane. In this study, we report another class of carrier proteins, termed Serinc1 - 5, that incorporates a polar amino acid serine into membranes and facilitates the synthesis of two serine- derived lipids, phosphatidylserine and sphingolipids. Serinc is a unique protein family that shows no amino acid homology to other proteins but is highly conserved among eukaryotes. The members contain 11 transmembrane domains, and rat Serinc1 protein co- localizes with lipid biosynthetic enzymes in endoplasmic reticulum membranes. A Serinc protein forms an intracellular complex with key enzymes involved in serine and sphingolipid biosyntheses, and both functions, serine synthesis and membrane incorporation, are linked to each other. In the rat brain, expression of Serinc1 and Serinc2 mRNA was rapidly up- regulated by kainate- induced seizures in neuronal cell layers of the hippocampus. In contrast, myelin throughout the brain is enriched with Serinc5, which was down-regulated in the hippocampus by seizures. These results indicate a novel mechanism linking neural activity and lipid biosynthesis.