Alpha-Tubulin Acetylation in Trypanosoma cruzi: A Dynamic Instability of Microtubules Is Required for Replication and Cell Cycle Progression.
Alpha-Tubulin Acetylation in Trypanosoma cruzi: A Dynamic Instability of Microtubules Is Required for Replication and Cell Cycle Progression.
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DOI：
10.3389/fcimb.2021.642271
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发表时间：
2021
影响因子：
5.7
通讯作者：
Serra E
中科院分区：
文献类型：
--
作者：
Alonso VL;Carloni ME;Gonçalves CS;Martinez Peralta G;Chesta ME;Pezza A;Tavernelli LE;Motta MCM;Serra E
锥虫的细胞骨架排列比大多数真核细胞中的细胞骨架排列更简单。然而，它是由稳定的微管精确组织和构成的。这些微管组成有丝分裂时的有丝分裂纺锤体、基体、鞭毛轴丝和膜下微管，它们相互连接并与质膜相连，沿寄生虫细胞体的中轴形成螺旋排列。克氏锥虫的表膜下微管、有丝分裂微管和轴丝微管被广泛乙酰化。 α-微管蛋白赖氨酸 (K) 40 上的乙酰化从低等真核生物到哺乳动物都是保守的，并且与微管稳定性相关。还已知K40乙酰化显着发生在真核生物的鞭毛、中心粒、纤毛、基体和有丝分裂纺锤体上。锥虫中的几种微管蛋白翻译后修饰（包括 K40 的乙酰化）已被分类，但这些修饰对微管动力学和寄生虫生物学的功能重要性仍然很大程度上未明确。最近在几种真核生物中鉴定出初级微管蛋白乙酰转移酶 Mec-17/ATAT，一种 Gcn5 相关的 N-乙酰转移酶。在这里，我们报道克氏锥虫 ATAT 在体内乙酰化 α-微管蛋白，并且能够自动乙酰化。 TcATAT 位于上鞭毛体的细胞骨架和鞭毛中，并与这些结构中的乙酰化 α-微管蛋白共定位。我们使用 T. cruzi 中的诱导型载体 pTcINDEX-GW 表达了带有 HA 标签的 TcATAT。 TcATAT 的过度表达会导致 α 微管蛋白乙酰化物质的水平增加，诱导形态和超微结构缺陷，尤其是在线粒体中，并导致上鞭毛体细胞周期进程停止，这与动质体分裂受损有关。最后，由于 TcATAT 过度表达，我们观察到寄生虫对微管解聚药物变得更加耐药。这些结果支持这样的观点：α-微管蛋白乙酰化水平在克氏锥虫细胞周期的正常进展中受到精细调节。
Trypanosomatids have a cytoskeleton arrangement that is simpler than what is found in most eukaryotic cells. However, it is precisely organized and constituted by stable microtubules. Such microtubules compose the mitotic spindle during mitosis, the basal body, the flagellar axoneme and the subpellicular microtubules, which are connected to each other and also to the plasma membrane forming a helical arrangement along the central axis of the parasite cell body. Subpellicular, mitotic and axonemal microtubules are extensively acetylated in Trypanosoma cruzi. Acetylation on lysine (K) 40 of α-tubulin is conserved from lower eukaryotes to mammals and is associated with microtubule stability. It is also known that K40 acetylation occurs significantly on flagella, centrioles, cilia, basal body and the mitotic spindle in eukaryotes. Several tubulin posttranslational modifications, including acetylation of K40, have been cataloged in trypanosomatids, but the functional importance of these modifications for microtubule dynamics and parasite biology remains largely undefined. The primary tubulin acetyltransferase was recently identified in several eukaryotes as Mec-17/ATAT, a Gcn5-related N-acetyltransferase. Here, we report that T. cruzi ATAT acetylates α-tubulin in vivo and is capable of auto-acetylation. TcATAT is located in the cytoskeleton and flagella of epimastigotes and colocalizes with acetylated α-tubulin in these structures. We have expressed TcATAT with an HA tag using the inducible vector pTcINDEX-GW in T. cruzi. Over-expression of TcATAT causes increased levels of the alpha tubulin acetylated species, induces morphological and ultrastructural defects, especially in the mitochondrion, and causes a halt in the cell cycle progression of epimastigotes, which is related to an impairment of the kinetoplast division. Finally, as a result of TcATAT over-expression we observed that parasites became more resistant to microtubule depolymerizing drugs. These results support the idea that α-tubulin acetylation levels are finely regulated for the normal progression of T. cruzi cell cycle.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
3.8
作者：
Fassolari, Matias;Alonso, Guillermo D.
通讯作者：
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动力学DNA复制：Brucei和Crithidia fasciculata之间的机械差异。
影响因子：
7.8
作者：
Ferguson, M L;Torri, A F;Perez-Morga, D;Ward, D C;Englund, P T
通讯作者：
Englund, P T
影响因子：
4
作者：
Gadadhar, Sudarshan;Bodakuntla, Satish;Janke, Carsten
通讯作者：
Janke, Carsten
DOI：
10.1073/pnas.1605397113
发表时间：
2016-11-15
影响因子：
11.1
作者：
Coombes, Courtney;Yamamoto, Ami;Gardner, Melissa K.
通讯作者：
Gardner, Melissa K.