A TGF-β type II receptor that associates with developmental transition in Haemonchus contortus in vitro

PLoS Negl Trop Dis. 2019 Dec 2;13(12):e0007913. doi: 10.1371/journal.pntd.0007913. eCollection 2019 Dec.

Abstract

Background: The TGF-β signalling pathway plays a key role in regulating dauer formation in the free-living nematode Caenorhabditis elegans, and previous work has shown that TGF-β receptors are involved in parasitic nematodes. Here, we explored the structure and function of a TGF-β type II receptor homologue in the TGF-β signalling pathway in Haemonchus contortus, a highly pathogenic, haematophagous parasitic nematode.

Methodology/principal findings: Amino acid sequence and phylogenetic analyses revealed that the protein, called Hc-TGFBR2 (encoded by the gene Hc-tgfbr2), is a member of TGF-β type II receptor family and contains conserved functional domains, both in the extracellular region containing cysteine residues that form a characteristic feature (CXCX4C) of TGF-β type II receptor and in the intracellular regions containing a serine/threonine kinase domain. The Hc-tgfbr2 gene was transcribed in all key developmental stages of H. contortus, with particularly high levels in the infective third-stage larvae (L3s) and male adults. Immunohistochemical results revealed that Hc-TGFBR2 was expressed in the intestine, ovary and eggs within the uterus of female adults, and also in the testes of male adults of H. contortus. Double-stranded RNA interference (RNAi) in this nematode by soaking induced a marked decrease in transcription of Hc-tgfbr2 and in development from the exsheathed L3 to the fourth-stage larva (L4) in vitro.

Conclusions/significance: These results indicate that Hc-TGFBR2 plays an important role in governing developmental processes in H. contortus via the TGF-β signalling pathway, particularly in the transition from the free-living to the parasitic stages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Female
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Haemonchus / growth & development*
  • Haemonchus / metabolism*
  • Immunohistochemistry
  • Male
  • Phylogeny
  • Protein Domains
  • Receptor, Transforming Growth Factor-beta Type II / genetics*
  • Receptor, Transforming Growth Factor-beta Type II / metabolism*
  • Signal Transduction

Substances

  • Receptor, Transforming Growth Factor-beta Type II

Grant support

This study was supported by the National Key Basic Research Program (973 program) of China (grant no. 2015CB150300) and the Fundamental Research Funds for the Central Universities (grant no. 2662017PY084) to M.H.; the Huazhong Agricultural University Scientific & Technological Self Innovation Foundation (Program no. 2015RC005), the Australian Research Council (ARC) and Yourgene Bioscience, Melbourne Water Corporation, the National Health and Medical Research Council (NHMRC) of Australiato R.B.G.; and the Natural Science Foundation of Hubei Province (Grant No. 2017CFA020) to M.H., R.F., Y.Z. and J.Z. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.