Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport
Deficiency in ethanolamine plasmalogen leads to altered cholesterol transport
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DOI：
10.1194/jlr.m200363-jlr200
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发表时间：
2003-01-01
影响因子：
6.5
通讯作者：
Liscum, L
中科院分区：
文献类型：
--
作者：
Munn, NJ;Arnio, E;Liscum, L
缩醛磷脂是乙醇胺和胆碱磷脂的主要亚类，其中sn-1位具有通过乙烯基醚键连接的长链脂肪醇。这些磷脂被认为在膜融合介导的事件中发挥作用。在这项研究中，我们调查的作用，乙醇胺缩醛原plasmenylethanolamine（PlsEtn）在中国仓鼠卵巢细胞突变体NRe1.4和NZel-1，其中有单基因缺陷的PlsEtn生物合成的细胞内胆固醇转运。我们发现，PlsEtn是必不可少的特定的胆固醇运输途径，从细胞表面或内吞隔室的酰基辅酶A/胆固醇酰基转移酶在内质网。胆固醇从内质网或内吞隔室的细胞表面的运动是正常的PlsEtn缺陷细胞。此外，囊泡运输是正常的PlsEtn缺陷的细胞，如测量的流体相内吞和胞吐，作为新合成的蛋白质的运动到细胞表面。突变胆固醇转运表型是由于缺乏PlsEtn，因为当NRe 1 -4细胞用编码缺失酶的cDNA转染或提供进入缺陷下游的PlsEtn生物合成途径的代谢中间体时，它得到了纠正。未来的工作必须确定缩醛磷脂对胆固醇转运到内质网的确切作用。
Plasmalogens are a major sub-class of ethanolamine and choline phospholipids in which the sn-1 position has a long chain fatty alcohol attached through a vinyl ether bond. These phospholipids are proposed to play a role in membrane fusion-mediated events. In this study, we investigated the role of the ethanolamine plasmalogen plasmenylethanolamine (PlsEtn) in intracellular cholesterol transport in Chinese hamster ovary cell mutants NRe1.4 and NZel-1, which have single gene defects in PlsEtn biosynthesis. We found that PlsEtn was essential for specific cholesterol transport pathways, those from the cell surface or endocytic compartments to acyl-CoA/cholesterol acyltransferase in the endoplasmic reticulum. The movement of cholesterol from the endoplasmic reticulum or endocytic compartments to the cell surface was normal in PlsEtn-deficient cells. Also, vesicle trafficking was normal in PlsEtn-deficient cells, as measured by fluid phase endocytosis and exocytosis, as was the movement of newly-synthesized proteins to the cell surface. The mutant cholesterol transport phenotype was due to the lack of PlsEtn, since it was corrected when NRe1-4 cells were transfected with a cDNA encoding the missing enzyme or supplied with a metabolic intermediate that enters the PlsEtn biosynthetic pathway downstream of the defect. Future work must determine the precise role that plasmalogens have on cholesterol transport to the endoplasmic reticulum.