ARL1 has an essential role in Tryponosoma brucei
ARL1 has an essential role in Tryponosoma brucei
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DOI：
10.1042/bst0330643
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发表时间：
2005-08-01
影响因子：
3.9
通讯作者：
Smith, DF
中科院分区：
文献类型：
--
作者：
Price, HP;Goulding, D;Smith, DF
肉豆蔻酰辅酶A蛋白：NMT（N-肉豆蔻酰转移酶）催化具有一系列功能的细胞蛋白质的N-肉豆蔻酰化，并且对于原生动物寄生虫，大型利什曼原虫和布氏锥虫的生存力至关重要。在我们确定NMT的必需下游靶点的研究中，我们集中于ARF（ADP-核糖基化因子）蛋白家族，因为具有降低的NMT活性的酿酒酵母突变体中的生长停滞与该组蛋白成员的修饰减少相关。我们已经确定了9个ARF/ARL（ARL代表ARF样）编码的T。brucei和T. cruzi和L.少校霸王布氏杆菌ARL 1蛋白仅在哺乳动物血流形式的寄生虫中表达，其中其定位于高尔基体。RNAi（RNA干扰）已被用于证明ARL 1是这些感染细胞的生存力所必需的。在细胞死亡之前，ARL 1蛋白的消耗导致高尔基体结构的解体和大量GPI（糖基磷脂酰肌醇）锚定的VSG（变体表面糖蛋白）胞吐到寄生虫表面的延迟。
Myristoyl-CoA protein:NMT (N-myristoyl transferase) catalyses the N-myristoylation of cellular proteins with a range of functions and is essential for viability in the protozoan parasites, Leishmania major and Trypanosoma brucei. in our investigations to define the essential downstream targets of NMT, we have focused on the ARF (ADP-ribosylation factor) family of proteins, as growth arrest in Saccharomyces cerevisiae mutants with reduced NMT activity correlates with decreased modification of members of this group of proteins. We have identified nine ARF/ARLs (where ARL stands for ARF-like) encoded in the T. brucei and T. cruzi genomes and ten in L. major. The T. brucei ARL1 protein is expressed only in the mammalian bloodstream form of the parasite, in which it is localized to the Golgi apparatus. RNAi (RNA interference) has been used to demonstrate that ARL1 is essential for viability in these infective cells. Before cell death, depletion of ARL1 protein results in disintegration of the Golgi structure and a delay in exocytosis of the abundant GPI (glycosylphosphatidylinositol)-anchored VSG (variant surface glycoprotein) to the parasite surface.