Aurora kinase protein family in Trypanosoma cruzi: Novel role of an AUK-B homologue in kinetoplast replication
Aurora kinase protein family in Trypanosoma cruzi: Novel role of an AUK-B homologue in kinetoplast replication
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DOI：
10.1371/journal.pntd.0007256
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发表时间：
2019-03-01
影响因子：
3.8
通讯作者：
Alonso, Guillermo D.
中科院分区：
文献类型：
--
作者：
Fassolari, Matias;Alonso, Guillermo D.
极光激酶是一个在后生动物细胞分裂过程中起关键作用的酶家族，参与着丝体成熟和分裂、染色质凝聚、有丝分裂纺锤体组装、着丝点-微管附着的控制以及细胞质分裂起始等事件。本研究在克氏锥虫中鉴定了3个极光激酶同源物（TcAUK1、-2和-3）。克氏锥虫是动质体纲的一种原生动物寄生虫。对这些酶的基因组组织进行了充分的分析，证明TcAUK1是单拷贝基因，TcAUK2编码序列有两种不同的形式（短和长），TcAUK3是多拷贝基因。这三种TcAUK基因在克氏体不同的生命周期形式（无尾、半乳和拟无尾）中均有活性表达。TcAUK1在增殖的附原体形式的细胞周期中显示出位置的变化：在间期，它位于着丝体的极端，而在有丝分裂时，它在细胞核中被检测到，与有丝分裂纺锤体密切相关。TcAUK1的过表达导致细胞周期的G2/M期延迟，这是由于动原体复制的延迟开始。通过免疫荧光，我们发现当TcAUK1过表达时，它在间期失去了在着丝体极端的定位，在整个细胞周期中都在细胞核内观察到。总之，TcAUK1似乎是人类Aurora B激酶的功能同源物，因为它与有丝分裂纺锤体组装和染色体分离有关。此外，TcAUK1似乎还在着丝体复制的起始过程中发挥作用，这是该蛋白的一个新功能。
Aurora kinases constitute a family of enzymes that play a key role during metazoan cells division, being involved in events like centrosome maturation and division, chromatin condensation, mitotic spindle assembly, control of kinetochore-microtubule attachments, and cytokinesis initiation. In this work, three Aurora kinase homologues were identified in Trypanosoma cruzi (TcAUK1, -2 and -3), a protozoan parasite of the Kinetoplastida Class. The genomic organization of these enzymes was fully analyzed, demonstrating that TcAUK1 is a single-copy gene, TcAUK2 coding sequence is present in two different forms (short and long) and TcAUK3 is a multi-copy gene. The three TcAUK genes are actively expressed in the different life cycle forms of T. cruzi (amastigotes, trypomastigotes and epimastigotes). TcAUK1 showed a changing localization along the cell cycle of the proliferating epimastigote form: at interphase it is located at the extremes of the kinetoplast while in mitosis it is detected at the cell nucleus, in close association with the mitotic spindle. Overexpression of TcAUK1 in epimastigotes leaded to a delay in the G2/M phases of the cell cycle due a retarded beginning of kinetoplast duplication. By immunofluorescence, we found that when it was overexpressed TcAUK1 lost its localization at the extremes of the kinetoplast during interphase, being observed inside the cell nucleus throughout the entire cell cycle. In summary, TcAUK1 appears to be a functional homologue of human Aurora B kinase, as it is related to mitotic spindle assembling and chromosome segregation. Moreover, TcAUK1 also seems to play a role during the initiation of kinetoplast duplication, a novel role described for this protein.