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Title: Calcium-dependent phospholipid scrambling by TMEM16F.
Authors: Suzuki, Jun  kyouindb  KAKEN_id
Umeda, Masato  kyouindb  KAKEN_id
Sims, Peter J
Nagata, Shigekazu  KAKEN_id
Author's alias: 鈴木, 淳
梅田, 眞郷
長田, 重一
Issue Date: 24-Nov-2010
Publisher: Nature Publishing Group
Journal title: Nature
Volume: 468
Issue: 7325
Start page: 834
End page: 838
Abstract: In all animal cells, phospholipids are asymmetrically distributed between the outer and inner leaflets of the plasma membrane. 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 system. The PtdSer exposure is believed to be mediated by Ca(2+)-dependent phospholipid scramblases that transport phospholipids bidirectionally, but its molecular mechanism is still unknown. Here we show that TMEM16F (transmembrane protein 16F) is an essential component for the Ca(2+)-dependent exposure of PtdSer on the cell surface. When a mouse B-cell line, Ba/F3, was treated with a Ca(2+) ionophore under low-Ca(2+) 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 segments. Wild-type TMEM16F was localized on the plasma membrane and conferred Ca(2+)-dependent scrambling of phospholipids. A patient with Scott syndrome, which results from a defect in phospholipid scrambling activity, was found to carry a mutation at a splice-acceptor site of the gene encoding TMEM16F, causing the premature termination of the protein.
Description: 血小板において止血の引き金となるリン脂質の暴露に関与する因子の同定-ヒトの遺伝病(スコット症候群)の原因遺伝子の同定. 京都大学プレスリリース. 2010-11-25.
Rights: 許諾条件により本文は2011-05-24に公開.
This is not the published version. Please cite only the published version.
DOI(Published Version): 10.1038/nature09583
PubMed ID: 21107324
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