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Nature:与磷脂拼接酶活性有关的一种蛋白

2010/12/09 来源:Nature 中文
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导读
真核细胞的质膜有不对称的磷脂分布。在细胞凋亡等生物过程中,类脂不对称性会被破坏,因为在这些过程中,膜内叶中的磷脂酰丝氨酸暴露在外膜上。曾有人提出,磷脂拼接酶的激发催化磷脂的双向跨双层运动,而现在,相应于这种活性的一种蛋白已被识别为TMEM16F,它是TMEM16跨膜蛋白家族的一员

真核细胞的质膜有不对称的磷脂分布。在细胞凋亡等生物过程中,类脂不对称性会被破坏,因为在这些过程中,膜内叶中的磷脂酰丝氨酸暴露在外膜上。曾有人提出,磷脂拼接酶的激发催化磷脂的双向跨双层运动,而现在,相应于这种活性的一种蛋白已被识别为TMEM16F,它是TMEM16跨膜蛋白家族的一员。而且,一位Scott综合症患者(患病原因是磷脂拼接活性存在缺陷)被发现在编码TMEM16F的基因中携带一个突变。

 

推荐原文出处:

Nature doi:10.1038/nature09583

Calcium-dependent phospholipid scrambling by TMEM16F

Jun Suzuki,Masato Umeda,Peter J. Sims" Shigekazu Nagata

In all animal cells, phospholipids are asymmetrically distributed between the outer and inner leaflets of the plasma membrane1. This asymmetrical phospholipid distribution is disrupted in various biological systems. For example, when blood platelets are activated, they expose phosphatidylserine (PtdSer) to trigger the clotting system2, 3. The PtdSer exposure is believed to be mediated by Ca2+-dependent phospholipid scramblases that transport phospholipids bidirectionally1, 4, but its molecular mechanism is still unknown. Here we show that TMEM16F (transmembrane protein 16F) is an essential component for the Ca2+-dependent exposure of PtdSer on the cell surface. When a mouse B-cell line, Ba/F3, was treated with a Ca2+ ionophore under low-Ca2+ conditions, it reversibly exposed PtdSer. Using this property, we established a Ba/F3 subline that strongly exposed PtdSer by repetitive fluorescence-activated cell sorting. A complementary DNA library was constructed from the subline, and a cDNA that caused Ba/F3 to expose PtdSer spontaneously was identified by expression cloning. The cDNA encoded a constitutively active mutant of TMEM16F, a protein with eight transmembrane segments5. Wild-type TMEM16F was localized on the plasma membrane and conferred Ca2+-dependent scrambling of phospholipids. A patient with Scott syndrome6, 7, which results from a defect in phospholipid scrambling activity8, 9, was found to carry a mutation at a splice-acceptor site of the gene encoding TMEM16F, causing the premature termination of the protein.

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