cGMP and NHR Signaling Co-regulate Expression of Insulin-Like Peptides and Developmental Activation of Infective Larvae in

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Human parasitic nematodes, including Strongyloides stercoralis, cause extensive morbidity in the developing world. The infectious form of S. stercoralis is a developmentally arrested third-stage larva (L3i), which resumes development into a parasitic adult upon entering a host. The molecular mechanisms controlling the developmental arrest and activation of L3i are not well understood. The free-living nematode Caenorhabditis elegans has a morphologically similar developmentally arrested third-stage dauer larva, which is regulated by four canonical dauer signaling pathways. Using C. elegans as a model, we hypothesized that cyclic guanosine monophosphate (cGMP) signaling would be important for L3i activation and would also regulate downstream insulin/IGF-1-like signaling (IIS). Indeed, we found that the membrane-permeable cGMP analog 8-bromo-cGMP stimulated L3i activation, accompanied by an increase in transcripts of putative agonistic insulin-like peptides (ILPs), which encode the ligands for IIS. Using the C. elegans model, we also hypothesized that DAF-12 nuclear hormone receptor (NHR) signaling would be downstream of IIS during L3i activation. Surprisingly, we found that during L3i activation, parallel cGMP and DAF-12 NHR signaling pathways co-regulate the downstream IIS pathway via modulation of ILPs. Together, these data help to further elucidate the pathways governing S. stercoralis L3i development.

Vyšlo v časopise: cGMP and NHR Signaling Co-regulate Expression of Insulin-Like Peptides and Developmental Activation of Infective Larvae in. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004235
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004235

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