The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice
The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice
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DOI：
10.1083/jcb.139.1.103
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发表时间：
1997-10-06
影响因子：
7.8
通讯作者：
Carrington, M
中科院分区：
文献类型：
--
作者：
Webb, H;Carnall, N;Carrington, M
在哺乳动物宿主中，布氏锥虫的细胞表面由一种变异表面糖蛋白保护，该糖蛋白通过其羧基末端与糖基磷脂酰肌醇共价连接而锚定在质膜上。锥虫还含有一种磷脂酶C（GPI - PLC），它能切割这种锚定结构，从而有可能使锥虫脱去变异表面糖蛋白（VSG）的表面外壳。实际上，在体外裂解锥虫后的几分钟内就可以观察到表面VSG的释放。为了研究切割VSG膜锚定结构的能力是否是该酶在体内的一项基本功能，通过靶向基因缺失产生了一种GPI - PLC缺失突变型锥虫。这种突变型锥虫完全具有活力；它们能够经历整个生命周期，并在小鼠体内维持持续感染。因此，GPI - PLC不是一种必需的活性，对抗原变异也不是必需的。然而，感染突变型锥虫的小鼠寄生虫血症水平降低，并且比感染对照锥虫的小鼠存活时间更长。当对缺失突变体进行改造使其表达低水平的GPI - PLC时，这种表型会部分缓解。
In the mammalian host, the cell surface of Trypanosoma brucei is protected by a variant surface glycoprotein that is anchored in the plasma membrane through covalent attachment of the COOH terminus to a glycosylphosphatidylinositol. The trypanosome also contains a phospholipase C (GPI-PLC) that cleaves this anchor and could thus potentially enable the trypanosome to shed the surface coat of VSG. Indeed, release of the surface VSG can be observed within a few minutes on lysis of trypanosomes in vitro. To investigate whether the ability to cleave the membrane anchor of the VSG is an essential function of the enzyme in vivo, a GPI-PLC null mutant trypanosome has been generated by targeted gene deletion. The mutant trypanosomes are fully viable; they can go through an entire life cycle and maintain a persistent infection in mice. Thus the GPI-PLC is not an essential activity and is not necessary for antigenic variation. However, mice infected with the mutant trypanosomes have a reduced parasitemia and survive longer than those infected with control trypanosomes. This phenotype is partially alleviated when the null mutant is modified to express low levels of GPI-PLC.