Molecular species of phosphatidylinositol-cycle intermediates in the endoplasmic reticulum and plasma membrane.
Molecular species of phosphatidylinositol-cycle intermediates in the endoplasmic reticulum and plasma membrane.
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DOI：
10.1021/bi901551e
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发表时间：
2010-01-19
期刊：
影响因子：
2.9
通讯作者：
Epand, Richard M.
中科院分区：
文献类型：
--
作者：
Shulga, Yulia V.;Myers, David S.;Ivanova, Pavlina T.;Milne, Stephen B.;Brown, H. Alex;Topham, Matthew K.;Epand, Richard M.
磷脂酰肌醇（PI）的转化是一个需要血浆和内质网膜共同参与的过程。我们用质谱法测定了磷脂酸（PA）和磷脂酸（PI）在这两种亚细胞膜中的分布及其酰基链组成。我们通过比较二酰基甘油激酶ε (DGKε)敲除（KO）和野生型（WT）小鼠胚胎成纤维细胞分离的两种膜的组成，评估PI循环在确定这些脂质的分子种类和数量中的作用。在KO细胞中，富含花生四烯酰基的DAG向PA的转化被DGKε的缺失所阻断，导致pi循环速率降低。内质网（ER）和质膜（PM）中的PI或PA的酰基链组成非常相似，WT和KO的酰基链组成也非常相似。然而，PI的酰基链分布与PA有很大的不同。这表明DGKε不促进特定种类PA在PM和ER之间的直接转移。内质网膜中约20%的PA具有一条14个或更少碳的短酰基链。这些PA不转化为PI，但可能在内质网高正曲率区域起稳定作用。在内质网和PM中也存在未检测到PA前体的PI物种，这表明这些PI物种不太可能通过PI循环产生。我们发现，在KO细胞的PM中，PI和PA的水平与WT细胞的PM或与KO细胞的ER相比下降了约三倍。在KO细胞中，pi周期被减慢，因此pi周期的脂质中间体不能再相互转化，并通过转化到其他物种而从pi周期中耗尽。与PM相比，在PA的重新合成发生的ER中，耗竭的影响较小。
Phosphatidylinositol (PI) turnover is a process requiring both the plasma and ER membranes. We have determined the distribution of phosphatidic acid (PA) and PI and their acyl chain compositions in these two subcellular membranes using mass spectrometry. We assessed the role of PI cycling in determining the molecular species and quantity of these lipids by comparing the compositions of the two membranes isolated from embryonic fibroblasts obtained from diacylglycerol kinase epsilon (DGKε) knock out (KO) and wild type (WT) mice. In the KO cells the conversion of arachidonoyl-rich DAG to PA is blocked by the absence of DGKε, resulting in reducing the rate of PI-cycling. The acyl chain composition is very similar for PI or PA in the endoplasmic reticulum (ER) vs. plasma membrane (PM) and for WT vs. KO. However, the acyl chain profile for PI is very different from that for PA. This indicates that DGKε is not facilitating the direct transfer of a specific species of PA between the PM and the ER. About 20% of the PA in the ER membrane has one short acyl chain of 14 carbons or less. These species of PA are not converted into PI but may play a role in stabilizing regions of high positive curvature in the ER. There are also PI species in both the ER and PM for which there is no detectable PA precursor, indicating that these species of PI are unlikely to arise via the PI-cycle. We find that in the PM of KO cells the levels of PI and of PA are decreased about three-fold in comparison with either the PM of WT cells or in comparison with the ER of KO cells. The PI-cycle is slowed in the KO cells, hence the lipid intermediates of the PI-cycle can no longer be interconverted and are depleted from the PI-cycle by conversion to other species. There is less of an effect of the depletion in the ER where de novo synthesis of PA occurs in comparison with the PM.
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影响因子：
2.9
作者：
Milne, Stephen B.;Ivanova, Pavlina T.;Armstrong, Michelle D.;Myers, David S.;Lubarda, Jovana;Shulga, Yulia V.;Topham, Matthew K.;Brown, H. Alex;Epand, Richard M.
通讯作者：
Epand, Richard M.
影响因子：
6.5
作者：
Shindou, Hideo;Hishikawa, Daisuke;Shimizu, Takao
通讯作者：
Shimizu, Takao
影响因子：
6.5
作者：
Fagone, Paolo;Jackowski, Suzanne
通讯作者：
Jackowski, Suzanne
DOI：
10.1016/j.bbalip.2006.03.016
发表时间：
2006-04-01
影响因子：
4.8
作者：
Ring, Axel;Le Lay, Soazig;Stremmel, Wolfgang
通讯作者：
Stremmel, Wolfgang
影响因子：
3.3
作者：
Huang, P;Altshuller, YM;Frohman, MA
通讯作者：
Frohman, MA