The endocytic activity of the flagellar pocket in Trypanosoma brucei is regulated by an adjacent phosphatidylinositol phosphate kinase

The endocytic activity of the flagellar pocket in Trypanosoma brucei is regulated by an adjacent phosphatidylinositol phosphate kinase
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DOI:
10.1242/jcs.146894
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发表时间:
2014-05-15
影响因子:
4
通讯作者:
Warren, Graham
Warren, Graham
中科院分区:
生物学2区
文献类型:
--
作者:
Demmel, Lars;Schmidt, Katy;Warren, Graham

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肌醇磷脂是空间受限的膜信号分子。磷脂酰肌醇4,5-二磷酸[PI(4,5)P-2]-一种在质膜中高度丰富并存在于整个质膜中的磷脂酰肌醇-与内吞作用有关。布鲁氏锥虫的内吞作用是已知的最高比率之一,它用来逃避免疫系统的过程。为了确定肌醇磷脂是否在这种生物的内吞作用中起作用,我们已经鉴定并鉴定了一种负责产生PI(4,5)P-2的酶。令人惊讶的是,这种肌醇磷脂被发现高度集中在鞭毛袋中,鞭毛袋是这种有机体唯一的内吞和胞吐的部位。这种酶(命名为TbPIPKA,注释为Tb927.10.1620)存在于寄生虫口袋的颈部,朝向寄生虫的前端。TbPIPKA的缺失导致PI(4,5)P-2的缺失和囊袋的增大,这是内吞作用受损的结果。综上所述,这些数据表明TbPIPKA及其产物PI(4,5)P-2对于内吞作用以及鞭毛袋的动态平衡是重要的。
Phosphoinositides are spatially restricted membrane signaling molecules. Phosphatidylinositol 4,5-bisphosphate [PI(4,5) P-2] - a phosphoinositide that is highly enriched in, and present throughout, the plasma membrane - has been implicated in endocytosis. Trypanosoma brucei has one of the highest known rates of endocytosis, a process it uses to evade the immune system. To determine whether phosphoinositides play a role in endocytosis in this organism, we have identified and characterized one of the enzymes that is responsible for generating PI(4,5) P-2. Surprisingly, this phosphoinositide was found to be highly concentrated in the flagellar pocket, the only site of endocytosis and exocytosis in this organism. The enzyme (designated TbPIPKA, annotated as Tb927.10.1620) was present at the neck of the pocket, towards the anterior-end of the parasite. Depletion of TbPIPKA led to depletion of PI(4,5) P-2 and enlargement of the pocket, the result of impaired endocytosis. Taken together, these data suggest that TbPIPKA and its product PI(4,5) P-2 are important for endocytosis and, consequently, for homeostasis of the flagellar pocket.