In vitro metacyclogenesis of Trypanosoma cruzi induced by starvation correlates with a transient adenylyl cyclase stimulation as well as with a constitutive upregulation of adenylyl cyclase expression
In vitro metacyclogenesis of Trypanosoma cruzi induced by starvation correlates with a transient adenylyl cyclase stimulation as well as with a constitutive upregulation of adenylyl cyclase expression
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DOI：
10.1016/j.molbiopara.2015.04.002
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发表时间：
2015-03-01
影响因子：
1.5
通讯作者：
Salmon, Didier
中科院分区：
文献类型：
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作者：
Hamedi, Afsaneh;Botelho, Larisse;Salmon, Didier
克氏锥虫腺苷酸环化酶 (AC) 多基因家族编码不同的亚型（约 15 种），共享可变的大 N 端结构域，该结构域是细胞外的和受体样的，随后是跨膜螺旋和保守的 C 端催化结构域。有人提出，cAMP 信号通路中的这些关键酶使寄生虫能够感知其变化的细胞外环境，以便快速适应其新环境，这通常是通过分化过程实现的。寄生原生动物克氏锥虫在其生命周期中经历的关键分化事件之一，称为后生，发生在昆虫的消化道中，对应于从非感染性上鞭毛体到感染性后循环锥鞭毛体形式的分化。通过体外监测宏发生过程中 AC 的活性，我们发现 AC 的活性和细胞内 cAMP 含量都遵循两步过程中类似的瞬时刺激模式，第一个激活峰值出现在营养应激的第一个小时内，第二个峰值出现在 6 至 48 小时之间，对应于细胞粘附。在此分化过程中，触发了 mRNA 和蛋白质 AC 表达上调的一般机制，特别是对于这些酶的主要亚类，这些酶存在于通常与 THT 基因簇相关的各种基因拷贝中。尽管这些基因拷贝的分散基因组分布在锥虫中相当不寻常，并且似乎是克氏锥虫进化枝中最近获得的，但它们的编码产物在分化时重新分布在寄生虫的鞭毛上，这对于感知细胞外环境可能很重要。 (C) 2015 Elsevier B.V. 保留所有权利。
The Trypanosoma cruzi adenylyl cyclase (AC) multigene family encodes different isoforms (around 15) sharing a variable large N-terminal domain, which is extracellular and receptor-like, followed by a transmembrane helix and a conserved C-terminal catalytic domain. It was proposed that these key enzymes in the cAMP signalling pathway allow the parasite to sense its changing extracellular milieu in order to rapidly adapt to its new environment, which is generally achieved through a differentiation process. One of the critical differentiation events the parasitic protozoan T. cruzi undergoes during its life cycle, known as metacyclogenesis, occurs in the digestive tract of the insect and corresponds to the differentiation from noninfective epimastigotes to infective metacyclic trypomastigote forms. By in vitro monitoring the activity of AC during metacyclogenesis, we showed that both the activity of AC and the intracellular cAMP content follow a similar pattern of transient stimulation in a two-step process, with a first activation peak occurring during the first hours of nutritional stress and a second peak between 6 and 48 h, corresponding to the cellular adhesion. During this differentiation process, a general mechanism of upregulation of AC expression of both mRNA and protein is triggered and in particular for a major subclass of these enzymes that are present in various gene copies commonly associated to the THT gene clusters. Although the scattered genome distribution of these gene copies is rather unusual in trypanosomatids and seems to be a recent acquisition in the evolution of the T. cruzi clade, their encoded product redistributed on the flagellum of the parasite upon differentiation could be important to sense the extracellular milieu. (C) 2015 Elsevier B.V. All rights reserved.