Lysophosphatidylinositol-acyltransferase-1 (LPIAT1) is required to maintain physiological levels of PtdIns and PtdInsP(2) in the mouse.
Lysophosphatidylinositol-acyltransferase-1 (LPIAT1) is required to maintain physiological levels of PtdIns and PtdInsP(2) in the mouse.
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DOI：
10.1371/journal.pone.0058425
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Hawkins PT
中科院分区：
文献类型：
--
作者：
Anderson KE;Kielkowska A;Durrant TN;Juvin V;Clark J;Stephens LR;Hawkins PT
我们在小鼠中干扰了编码溶血磷脂酰肌醇-酰基转移酶-1(LPIAT1)的基因，目的是了解它在确定细胞磷脂酰肌醇含量中的作用。LPIAT1−/−小鼠出生时的比例低于孟德尔比例，并表现出严重的脑发育缺陷。我们用LC-ESI/MS比较了LPIAT1−/−和LPIAT1+/+的肝脏和大脑的磷脂含量。与以前的研究一致，每一类磷脂酰肌醇中最丰富的分子物种(PtdIns、PtdInsP、PtdInsP2和PtdInsP3)都含有C38：4的脂肪酸酯(C18：0和C20：4通常分别位于sn-1和sn-2位)。LPIAT1−/−肝脏和脑中含有相对较少的C38：4种PtdIns、PtdInsP和PtdInsP2(从每种脂类测量的总物种的95%-97%下降到75%-85%)，而相对较少的物种(PtdInsP3含量较低的物种低于我们的量化水平)。数量较少的PtdIns和PtdInsP2物种的增加不能弥补C38：4物种的损失，导致脑和肝脏中总PtdIns和PtdInsP2水平下降26-44%。LPIAT1、−/−、脑和肝脏的C18：0Lyso-PtdIns水平也升高(分别为300%和525%)，表明该分子的反应有缺陷。此外，LPIAT1−/−脑中还含有显著降低的C38：4 PC和PE水平(分别降低了47%和55%)，这可能与该器官的表型有关。在LPIAT1−/−和LPIAT1+/+样本中，在脑和肝脏中测得的PC、PE、PS和PA的所有其他分子物种的水平非常相似。这些结果表明，在小鼠组织中，LPIAT1活性在维持PtdIns在活跃的脱酰/反应循环中的生理水平方面起着非多余的作用。他们还提出，这一途径必须与其他尚未确定的机制协同作用，以实现在c38：4磷脂酰肌醇分子物种中观察到的浓缩。
We disrupted the gene encoding lysophosphatidylinositol-acyltransferase-1 (LPIAT1) in the mouse with the aim of understanding its role in determining cellular phosphoinositide content. LPIAT1−/− mice were born at lower than Mendelian ratios and exhibited a severe developmental brain defect. We compared the phospholipid content of livers and brains from LPIAT1−/− and LPIAT1+/+ littermates by LC-ESI/MS. In accord with previous studies, the most abundant molecular species of each phosphoinositide class (PtdIns, PtdInsP, PtdInsP2 and PtdInsP3) possessed a C38∶4 complement of fatty-acyl esters (C18∶0 and C20∶4 are usually assigned to the sn-1 and sn-2 positions, respectively). LPIAT1−/− liver and brain contained relatively less of the C38∶4 species of PtdIns, PtdInsP and PtdInsP2 (dropping from 95–97% to 75–85% of the total species measured for each lipid class) and relatively more of the less abundant species (PtdInsP3 less abundant species were below our quantification levels). The increases in the less abundant PtdIns and PtdInsP2 species did not compensate for the loss in C38∶4 species, resulting in a 26–44% reduction in total PtdIns and PtdInsP2 levels in both brain and liver. LPIAT1−/− brain and liver also contained increased levels of C18∶0 lyso-PtdIns (300% and 525% respectively) indicating a defect in the reacylation of this molecule. LPIAT1−/− brain additionally contained significantly reduced C38∶4 PC and PE levels (by 47% and 55% respectively), possibly contributing to the phenotype in this organ. The levels of all other molecular species of PC, PE, PS and PA measured in the brain and liver were very similar between LPIAT1−/− and LPIAT1+/+ samples. These results suggest LPIAT1 activity plays a non-redundant role in maintaining physiological levels of PtdIns within an active deacylation/reacylation cycle in mouse tissues. They also suggest that this pathway must act in concert with other, as yet unidentified, mechanisms to achieve the enrichment observed in C38∶4 molecular species of phosphoinositides.
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影响因子：
3.3
作者：
Lee HC;Inoue T;Sasaki J;Kubo T;Matsuda S;Nakasaki Y;Hattori M;Tanaka F;Udagawa O;Kono N;Itoh T;Ogiso H;Taguchi R;Arita M;Sasaki T;Arai H
通讯作者：
Arai H
影响因子：
6.5
作者：
Shindou, Hideo;Hishikawa, Daisuke;Shimizu, Takao
通讯作者：
Shimizu, Takao
DOI：
10.1042/bj20090428
发表时间：
2009-07-29
期刊：
The Biochemical journal
影响因子：
--
作者：
Hammond GR;Schiavo G;Irvine RF
通讯作者：
Irvine RF
影响因子：
2.9
作者：
Rouzer, Carol A.;Ivanova, Pavlina T.;Marnett, Lawrence J.
通讯作者：
Marnett, Lawrence J.
影响因子：
6.5
作者：
Pettitt, Trevor R.;Dove, Stephen K.;Wakelam, Michael J. O.
通讯作者：
Wakelam, Michael J. O.