通过TMEM16F进行依赖脂杂
Jun Suzuki1, Masato Umeda, Peter J Sims
1Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Nature
|November 26, 2010
概括
跨膜蛋白16F (TMEM16F) 对于细胞表面的依赖性胺素 (PtdSer) 暴露至关重要. TMEM16F中的突变会导致斯科特综合征,这种疾病与缺陷的脂杂乱有关.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 膜生物物理学 膜生物物理学
背景情况:
- 脂在动物细胞等离子体膜中分布不对称.
- 破坏的脂不对称性,比如酸丁素 (PtdSer) 暴露在活化血小板上,会触发诸如血液凝结等生物过程.
- 由scramblases介导的Ca(2+) 依存的脂杂乱的分子机制在很大程度上是未知的.
研究的目的:
- 为了确定负责Ca(2+) 依赖的酸胺 (PtdSer) 暴露的分子成分.
- 阐明细胞系统中脂混杂背后的机制.
主要方法:
- 使用用于增强PtdSer暴露的小鼠B细胞系 (Ba/F3) 的表达克隆.
- TMEM16F.的位点定向突变发生和功能测定.
- 对一个携带TMEM16F基因突变的斯科特综合征患者的分析.
主要成果:
- 确定TMEM16F是Ca(2+) 依存的PtdSer暴露的重要组成部分.
- 一种构成性活跃的TMEM16F突变诱导了自发的PtdSer暴露.
- 野生型TMEM16F定位在血上,并通过Ca(2+) 介导依赖脂混杂.
- 一名斯科特综合征患者表现出TMEM16F突变,导致过早的蛋白质终止.
结论:
- TMEM16F是调节脂不对称性和PtdSer暴露的关键参与者.
- TMEM16F作为一个Ca(2+) 依存的脂混杂酶起作用.
- 在TMEM16F的缺陷直接涉及到斯科特综合征,突出其临床相关性.
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