Reconstruction of the insulin-like signalling pathway of Haemonchus contortus

Abstract

Background: In the present study, we reconstructed the insulin/insulin-like growth factor 1 signalling (IIS) pathway for Haemonchus contortus, which is one of the most important eukaryotic pathogens of livestock worldwide and is related to the free-living nematode Caenorhabditis elegans.

Methods: We curated full-length open-reading frames from assembled transcripts, defined the complement of genes that encode proteins involved in this pathway and then investigated the transcription profiles of these genes for all key developmental stages of H. contortus.

Results: The core components of the IIS pathway are similar to their respective homologs in C. elegans. However, there is considerable variation in the numbers of isoforms between H. contortus and C. elegans and an absence of AKT-2 and DDL-2 homologs from H. contortus. Interestingly, DAF-16 has a single isoform in H. contortus compared with 12 in C. elegans, suggesting novel functional roles in the parasitic nematode. Some IIS proteins, such as DAF-18 and SGK-1, vary in their functional domains, indicating distinct roles from their homologs in C. elegans.

Conclusions: This study paves the way for the further characterization of key signalling pathways in other socioeconomically important parasites and should help understand the complex mechanisms involved in developmental processes.

Fig. 1

Heat-map displaying transcription profiles for genes (cf. Table 1) involved in insulin/insulin-like growth factor 1 (IGF1)-like signalling (IIS) in Haemonchus contortus. Hc-ins-1a/1b, −ins-17 and -ins-18 are genes that act upstream (U) of the IIS pathway. Genes Hc-daf-2, −ist-1, −aap-1, −age-1a/1b, −daf-18, −pdk-1, −sgk-1a/1b, −akt-1a/1b, −pptr-1a/1b/1c, −pptr-2, −ftt-2, −par-5 and Hc-daf-16 are part of the core (C) IIS pathway and genes Hc-skn-1, −hsf-1a/1b, −hsb-1, −ddl-1 and Hc-egl-9a/b/c/d are activated downstream (D) of the IIS pathway. Transcription levels in different developmental stages (egg, L1, L2, L3, L4 and A = adult; f = female; m = male) of H. contortus (see colour scale): low (red), medium (orange), high (yellow) and very high (white)

Fig. 2

Reconstruction of the insulin/insulin-like growth factor 1 (IGF1)-like signalling (IIS) pathway of Haemonchus contortus. Four insulin-like peptides (ILPs) are encoded in H. contortus (orange) compared with 40 in Caenorhabditis elegans. All core functional gene products (green) of the IIS pathway, except for AKT-2 and DDL-2 (grey), are encoded in H. contortus. Additional transcription factors activated downstream of the IIS pathway, such as SKN-1 and HSF-1, are also predicted in H. contortus. Phosphatidylinositol (3,4,5)-trisphosphate (PIP₃) is the product of the class I phosphoinostide 3-kinases (PI 3-kinases) phosphorylation of phosphatidylinositol (4,5)-bisphosphate (PIP₂); it is a phospholipid in the plasma membrane. Phosphorylation represented by P (yellow). The insulin pathway controls the transcription of various genes, and regulates key processes, including dauer formation, longevity, stress resistance and morphogenesis, as well as other pathways such as TGF-β and involving other key transcription factors