Proteomic identification of novel cytoskeletal proteins associated with TbPLK, an essential regulator of cell morphogenesis in Trypanosoma brucei.
Proteomic identification of novel cytoskeletal proteins associated with TbPLK, an essential regulator of cell morphogenesis in Trypanosoma brucei.
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DOI：
10.1091/mbc.e15-04-0219
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发表时间：
2015-09-01
影响因子：
3.3
通讯作者：
de Graffenried CL
中科院分区：
文献类型：
--
作者：
McAllaster MR;Ikeda KN;Lozano-Núñez A;Anrather D;Unterwurzacher V;Gossenreiter T;Perry JA;Crickley R;Mercadante CJ;Vaughan S;de Graffenried CL
布氏锥虫Polo样激酶同源物是寄生虫细胞骨架的重要形态发生调节因子。一系列的蛋白质组学筛选确定了潜在的TbPLK结合伙伴和底物，并更好地说明了激酶的功能，产生新的蛋白质参与鞭毛定位。布氏锥虫是非洲昏睡病的病原体，非洲昏睡病是撒哈拉以南非洲的一种毁灭性地方病，几乎没有有效的治疗方法。该寄生虫是高度极化的，包括单个鞭毛，其在细胞后部成核并沿沿着细胞表面。这些特征是必不可少的，必须在分裂过程中传递给子细胞。最近，我们发现了T。布氏菌polo样激酶（TbPLK）同源物作为一种重要的形态发生调节因子。在目前的工作中，我们进行蛋白质组学筛选，以确定潜在的TbPLK结合伙伴和底物，以更好地了解激酶功能的分子机制。这些筛选鉴定了一组蛋白质，其中大部分是完全未表征的，其定位于参与建立细胞形态的关键细胞骨架细胞器，包括鞭毛连接器、鞭毛附着区和双叶结构。这些蛋白质的缺失导致细胞分裂的实质性变化，包括动质体的错位、鞭毛连接的丧失和胞质分裂的阻止。在这些筛选中鉴定的蛋白质为建立TbPLK指导T.布鲁塞。
The Trypanosoma brucei polo-like kinase homologue is an essential morphogenic regulator of the parasite's cytoskeleton. A series of proteomic screens identifies potential TbPLK binding partners and substrates and better illustrates how the kinase functions, yielding novel proteins involved in flagellar positioning. Trypanosoma brucei is the causative agent of African sleeping sickness, a devastating disease endemic to sub-Saharan Africa with few effective treatment options. The parasite is highly polarized, including a single flagellum that is nucleated at the posterior of the cell and adhered along the cell surface. These features are essential and must be transmitted to the daughter cells during division. Recently we identified the T. brucei homologue of polo-like kinase (TbPLK) as an essential morphogenic regulator. In the present work, we conduct proteomic screens to identify potential TbPLK binding partners and substrates to better understand the molecular mechanisms of kinase function. These screens identify a cohort of proteins, most of which are completely uncharacterized, which localize to key cytoskeletal organelles involved in establishing cell morphology, including the flagella connector, flagellum attachment zone, and bilobe structure. Depletion of these proteins causes substantial changes in cell division, including mispositioning of the kinetoplast, loss of flagellar connection, and prevention of cytokinesis. The proteins identified in these screens provide the foundation for establishing the molecular networks through which TbPLK directs cell morphogenesis in T. brucei.