Strongyloides stercoralis daf-2 encodes a divergent ortholog of Caenorhabditis elegans DAF-2

• Strongyloides stercoralis daf-2 encodes a divergent insulin-like receptor tyrosine kinase.
• Amino acid changes Q1242 and Q1256 in Ss-DAF-2 would be deleterious in other species.
• The Ss-daf-2 is expressed in two splice isoforms, daf-2a (exons 1 + 3) and daf-2b (exons 1 + 2 + 3).
• Exon-2 in Ss-daf-2b is located in a position that may alter ligand binding specificity or affinity.
• Ss-daf-2a is expressed at all life stages; daf-2b is only expressed in stages leading to parasitism.

We hypothesise that developmental arrest in infectious larvae of parasitic nematodes is regulated by signalling pathways homologous to Caenorhabditis elegans DAF (dauer formation) pathways. Alignment of Strongyloides stercoralis (Ss) DAF-2 with DAF-2 of C. elegans and homologs of other species shows that most structural motifs in these insulin-like receptors are conserved. However, the catalytic domain of Ss-DAF-2 contains two substitutions (Q1242 and Q1256), that would result in constitutive dauer formation in C. elegans or diabetes in vertebrate animals. Ss-daf-2 also shows two alternately spliced isoforms, the constitutively expressed Ss-daf-2a, and Ss-daf-2b, which is only expressed in stages leading to parasitism.

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