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Divergent Axin and GSK-3 paralogs in the beta-catenin destruction complexes of tapeworms.
Development Genes and Evolution ( IF 0.8 ) Pub Date : 2019-04-30 , DOI: 10.1007/s00427-019-00632-w
Jimena Montagne 1 , Matías Preza 1 , Estela Castillo 2 , Klaus Brehm 3 , Uriel Koziol 1
Affiliation  

The Wnt/beta-catenin pathway has many key roles in the development of animals, including a conserved and central role in the specification of the primary (antero-posterior) body axis. The posterior expression of Wnt ligands and the anterior expression of secreted Wnt inhibitors are known to be conserved during the larval metamorphosis of tapeworms. However, their downstream signaling components for Wnt/beta-catenin signaling have not been characterized. In this work, we have studied the core components of the beta-catenin destruction complex of the human pathogen Echinococcus multilocularis, the causative agent of alveolar echinococcosis. We focused on two Axin paralogs that are conserved in tapeworms and other flatworm parasites. Despite their divergent sequences, both Axins could robustly interact with one E. multilocularis beta-catenin paralog and limited its accumulation in a heterologous mammalian expression system. Similarly to what has been described in planarians (free-living flatworms), other beta-catenin paralogs showed limited or no interaction with either Axin and are unlikely to function as effectors in Wnt signaling. Additionally, both Axins interacted with three divergent GSK-3 paralogs that are conserved in free-living and parasitic flatworms. Axin paralogs have highly segregated expression patterns along the antero-posterior axis in the tapeworms E. multilocularis and Hymenolepis microstoma, indicating that different beta-catenin destruction complexes may operate in different regions during their larval metamorphosis.

中文翻译:

tape虫的β-catenin破坏复合物中的不同Axin和GSK-3旁系同源物。

Wnt /β-catenin途径在动物发育中具有许多关键作用,包括在主要(前后)体轴规格中的保守和重要作用。已知在tape虫的幼虫变态过程中,Wnt配体的后向表达和分泌的Wnt抑制剂的前向表达是保守的。但是,它们的Wnt /β-catenin信号传导下游信号成分尚未被表征。在这项工作中,我们研究了人类病原体多齿棘球,虫(肺泡棘球co病的病原体)的β-连环蛋白破坏复合物的核心成分。我们重点研究了在tape虫和其他扁虫寄生虫中保守的两种Axin同源物。尽管它们的序列不同,但两种毒素都可以与一种E. multilocularisβ -catenin旁系同源物并限制其在异源哺乳动物表达系统中的积累。与在涡虫(自由生活的扁虫)中描述的类似,其他β-连环蛋白旁系同源物显示与Axin的相互作用有限或没有相互作用,并且不太可能在Wnt信号传导中发挥效应子的作用。此外,两种毒素都与在自由生活和寄生扁虫中保守的三个不同的GSK-3旁系同源物相互作用。Axin旁系同源物在theE. multilocularisHymenolepis microstoma中沿前后轴高度分离的表达模式,表明不同的β-catenin破坏复合物在其幼虫变态期间可能在不同区域起作用。
更新日期:2019-04-30
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