Journal of Proteomics ( IF 2.8 ) Pub Date : 2020-08-14 , DOI: 10.1016/j.jprot.2020.103939 Jeferson Camargo de Lima 1 , Maiara Anschau Floriani 2 , João Antônio Debarba 3 , Gabriela Prado Paludo 1 , Karina Mariante Monteiro 4 , Hercules Moura 5 , John R Barr 5 , Arnaldo Zaha 3 , Henrique Bunselmeyer Ferreira 4
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Mesocestoides corti (syn. vogae) is a useful model for developmental studies of platyhelminth parasites of the Cestoda class, such as Taenia spp. or Echinococcus spp. It has been used in studies to characterize cestode strobilation, i.e. the development of larvae into adult worms. So far, little is known about the initial molecular events involved in cestode strobilation and, therefore, we carried out a study to characterize newly synthesized (NS) proteins upon strobilation induction. An approach based on bioorthogonal noncanonical amino acid tagging and mass spectrometry was used to label, isolate, identify, and quantify NS proteins in the initial steps of M. corti strobilation. Overall, 121 NS proteins were detected exclusively after induction of strobilation, including proteins related to development pathways, such as insulin and notch signaling. Metabolic changes that take place in the transition from the larval stage to adult worm were noted in special NS protein subsets related to developmental processes, such as focal adhesion, cell leading edge, and maintenance of location. The data shed light on mechanisms underlying early steps of cestode strobilation and enabled identification of possible developmental markers. We also consider the use of developmental responsive proteins as potential drug targets for developing novel anthelmintics.
Biological significance
Larval cestodiases are life-threatening parasitic diseases that affect both man and domestic animals worldwide. Cestode parasites present complex life cycles, in which they undergo major morphological and physiological changes in the transition from one life-stage to the next. One of these transitions occurs during cestode strobilation, when the mostly undifferentiated and non-segmented larval or pre-adult form develops into a fully segmented and sexually differentiated (strobilated) adult worm. Although the proteomes of bona fide larvae and strobialted adults have been previously characterized for a few cestode species, little is still known about the dynamic of protein synthesis during the early steps of cestode strobilation. Now, the assessment of newly synthesized (NS) proteins within the first 48 h of strobilation the model cestode M. corti allowed to shed light on molecular mechanisms that are triggered by strobilation induction. The functional analyses of this repertoire of over a hundred NS proteins pointed out to changes in metabolism and activation of classical developmental signaling pathways in early strobilation. Many of the identified NS proteins may become valuable cestode developmental markers and their involvement in vital processes make them also good candidate targets for novel anthelmintic drugs.
中文翻译：
绦虫模型寄生虫 Mesocestoides corti (syn. vogae) 初始阶段的蛋白质合成动力学。
Mesocestoides corti（syn. vogae）是绦虫纲扁形动物寄生虫（如绦虫属）发育研究的有用模型。或棘球绦虫属。它已被用于研究绦虫的发育特征，即幼虫发育成成虫的过程。到目前为止，人们对绦虫 strobilation 涉及的初始分子事件知之甚少，因此，我们进行了一项研究来表征 strobilation 诱导时新合成的 (NS) 蛋白质。基于生物正交非规范氨基酸标记和质谱的方法用于在M. corti strobillation 的初始步骤中标记、分离、识别和量化 NS 蛋白。总体而言，在诱导 strobillation 后仅检测到 121 种 NS 蛋白，包括与发育途径相关的蛋白，例如胰岛素和 Notch 信号传导。从幼虫阶段到成虫阶段发生的代谢变化在与发育过程相关的特殊 NS 蛋白亚群中被注意到，例如粘着斑、细胞前缘和位置维持。这些数据揭示了绦虫早期步骤的潜在机制，并能够识别可能的发育标记。我们还考虑使用发育反应蛋白作为开发新型驱虫药的潜在药物靶点。
生物学意义
幼虫绦虫病是一种危及生命的寄生虫病，影响全世界的人类和家畜。绦虫寄生虫具有复杂的生命周期，在从一个生命阶段到下一生命阶段的过渡过程中，它们经历了重大的形态和生理变化。其中一个转变发生在绦虫节育过程中，此时大部分未分化和不分节的幼虫或前成虫形式发育成完全分节和性分化（节育）的成虫。尽管之前已经对一些绦虫物种的真正幼虫和绦虫成虫的蛋白质组进行了表征，但对于绦虫早期步骤中蛋白质合成的动态仍然知之甚少。现在，对模型绦虫M. corti模型在 strobilation 的前 48 小时内新合成的 (NS) 蛋白质进行评估，可以揭示由 strobilation 诱导触发的分子机制。对一百多个 NS 蛋白的功能分析指出了早期 strobillation 中经典发育信号通路的代谢和激活的变化。许多已鉴定的 NS 蛋白可能成为有价值的绦虫发育标记物，它们参与生命过程，使它们成为新型驱虫药物的良好候选靶点。
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