ATP8A1 activity and phosphatidylserine transbilayer movement.
ATP8A1 activity and phosphatidylserine transbilayer movement.
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DOI：
10.2147/jrlcr.s3773
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发表时间：
2008-09
期刊：
影响因子：
--
通讯作者：
E. Soupene;D. Kemaladewi;F. Kuypers
中科院分区：
文献类型：
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作者：
E. Soupene;D. Kemaladewi;F. Kuypers
含氨基磷脂，磷脂酰丝氨酸（PS）和磷脂酰乙醇胺（PE）的不对称分布在红细胞（RBC）膜的两个小叶上，对细胞的功能和存活至关重要。PS和PE通过一种被称为RBC翻转酶的膜蛋白的atp依赖的运输活性被隔离在内小叶中，该酶特异性地将氨基磷脂从外小叶转移到内小叶。去核的红细胞缺乏替代受损酶的手段，而翻转酶的失活可导致PS在细胞表面的不正当暴露。在红细胞疾病中，维持磷脂不对称能力的丧失会加剧，而循环中暴露ps的红细胞在血红蛋白病的病理中起着重要作用。我们确定了Atp8a1蛋白，作为P(4)型ATPases家族的一员，作为RBC翻转酶的候选。Atp8a1在红细胞前体中表达，并存在于成熟红细胞的细胞膜中。在纯化的酿酒酵母分泌囊泡中建立了该蛋白的翻转酶活性。PS和PE刺激了atp酶活性。此外，在ATP存在的情况下，Atp8a1可以使PS分子穿过囊泡膜的小叶。
The asymmetric distribution of the amino-containing phospholipids, phosphatidyl-serine (PS) and phosphatidyl-ethanolamine (PE), across the two leaflets of red blood cell (RBC) membrane is essential to the function and survival of the cell. PS and PE are sequestered in the inner leaflet by an ATP-dependent transport activity of a membrane protein known as the RBC flippase that specifically moves amino-phospholipids from the outer to the inner leaflet. The enucleated RBC lacks the means to replace damaged enzymes and inactivation of the flippase can lead to the unwarranted exposure of PS on the cell surface. Loss in the ability to maintain phospholipid asymmetry is exacerbated in RBC disorders and PS-exposing RBCs present in the circulation play a significant role in the pathology of hemoglobinopathies. We identified the Atp8a1 protein, a member of the family of the P(4)-type ATPases, as a RBC flippase candidate. Atp8a1 is expressed in RBC precursors and is present in the membrane of mature red cells. The flippase activity of the protein was established in purified secretory vesicles of Saccharomyces cerevisiae. ATPase activity was stimulated by PS and PE. In addition, Atp8a1 can move PS molecules across the leaflets of the vesicle membrane in presence of ATP.