Divergent Axin and GSK-3 paralogs in the beta-catenin destruction complexes of tapeworms
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.
KeywordsWnt signaling Cestode Axin B-Catenin Glycogen Synthase Kinase-3
This work was supported by the Agencia Nacional de Investigación e Innovación (ANII), Uruguay, Grant FCE_2016_125588 (to U.K.) and by the Programa de Desarrollo de las Ciencias Básicas (PEDECIBA), Uruguay. Further support was provided by the Wellcome Trust, grant number 107475/Z/15/Z (to K.B.).
Compliance with ethical standards
Animal experiments were carried out in accordance with European and German regulations on the protection of animals (Tierschutzgesetz). Ethical approval of the study was obtained from the local ethics committee of the government of Lower Franconia, Germany (permit no. 55.2 DMS 2532-2-354) and Comisión Honoraria de Experimentación Animal, Uruguay (Protocol number 10190000025215) .
- Abramoff M, Magalhaes P, Ram S (2004) Image processing with ImageJ. Biophoton Int 11:36–42Google Scholar
- Howe KL, Bolt BJ, Cain S, Chan J, Chen WJ, Davis P, Done J, Down T, Gao S, Grove C, Harris TW, Kishore R, Lee R, Lomax J, Li Y, Muller HM, Nakamura C, Nuin P, Paulini M, Raciti D, Schindelman G, Stanley E, Tuli MA, van Auken K, Wang D, Wang X, Williams G, Wright A, Yook K, Berriman M, Kersey P, Schedl T, Stein L, Sternberg PW (2016) WormBase 2016: expanding to enable helminth genomic research. Nucleic Acids Res 44:D774–D780. https://doi.org/10.1093/nar/gkv1217 CrossRefGoogle Scholar
- Rui Y, Xu Z, Xiong B, Cao Y, Lin S, Zhang M, Chan SC, Luo W, Han Y, Lu Z, Ye Z, Zhou HM, Han J, Meng A, Lin SC (2007) A β-catenin-independent dorsalization pathway activated by Axin/JNK signaling and antagonized by Aida. Dev Cell 13:268–282. https://doi.org/10.1016/j.devcel.2007.07.006 CrossRefGoogle Scholar
- Smyth JD, McManus DP (2007) The physiology and biochemistry of cestodes. Cambridge University Press, CambridgeGoogle Scholar