Soupene Eric, Fyrst Henrik, Kuypers Frans A
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):88-93. doi: 10.1073/pnas.0709737104. Epub 2007 Dec 21.
The mammalian RBC lacks de novo lipid synthesis but maintains its membrane composition by rapid turnover of acyl moieties at the sn-2 position of phospholipids. Plasma-derived fatty acids are esterified to acyl-CoA by acyl-CoA synthetases and transferred to lysophospholipids by acyl-CoA:lysophospholipid acyltransferases. We report the characterization of three lysophosphatidylcholine (lysoPC) acyltransferases (LPCATs), products of the AYTL1, -2, and -3 genes. These proteins are three members of a LPCAT family, of which all three genes are expressed in an erythroleukemic cell line. Aytl2 mRNA was detected in mouse reticulocytes, and the presence of the product of the human ortholog was confirmed in adult human RBCs. The three murine Aytl proteins generated phosphatidylcholine from long-chain acyl-CoA and lysoPC when expressed in Escherichia coli membranes. Spliced variants of Aytl1, affecting a conserved catalytic motif, were identified. Calcium and magnesium modulated LPCAT activity of both Aytl1 and -2 proteins that exhibit EF-hand motifs at the C terminus. Characterization of the product of the Aytl2 gene as the phosphatidylcholine reacylating enzyme in RBCs represents the identification of a plasma membrane lysophospholipid acyltransferase and establishes the function of a LPCAT protein.
哺乳动物红细胞缺乏从头合成脂质的能力，而是通过磷脂sn-2位酰基部分的快速周转来维持其膜组成。血浆来源的脂肪酸通过酰基辅酶A合成酶酯化为酰基辅酶A，并通过酰基辅酶A：溶血磷脂酰基转移酶转移到溶血磷脂上。我们报道了三种溶血磷脂酰胆碱（lysoPC）酰基转移酶（LPCATs）的特性，它们是AYTL1、-2和-3基因的产物。这些蛋白质是LPCAT家族的三个成员，其中所有三个基因都在一种红白血病细胞系中表达。在小鼠网织红细胞中检测到Aytl2 mRNA，并且在成人红细胞中证实了人类直系同源物产物的存在。当在大肠杆菌膜中表达时，三种小鼠Aytl蛋白可从长链酰基辅酶A和lysoPC生成磷脂酰胆碱。鉴定出了影响保守催化基序的Aytl1剪接变体。钙和镁调节Aytl1和-2蛋白的LPCAT活性，这两种蛋白在C末端具有EF手基序。将Aytl2基因的产物鉴定为红细胞中的磷脂酰胆碱再酰化酶，代表了一种质膜溶血磷脂酰基转移酶的鉴定，并确立了LPCAT蛋白的功能。
