Identification of a nuclear receptor/coactivator developmental signaling pathway in the nematode parasite Strongyloides stercoralis

Mi Cheong Cheong, Zhu Wang, Tegegn G. Jaleta, Xinshe Li, James B. Lok, Steven A Kliewer, David J. Mangelsdorf

Research output: Contribution to journalArticlepeer-review

Abstract

DAF-12 is nematode-specific nuclear receptor that has been proposed to govern development of the infectious stage of parasitic species, including Strongyloides stercoralis. Here, we identified a parasite-specific coactivator, called DAF-12 interacting protein-1 (DIP-1), that is required for DAF-12 ligand-dependent transcriptional activity. DIP-1 is found only in Strongyloides spp. and selectively interacts with DAF-12 through an atypical receptor binding motif. Using CRISPR/Cas9-directed mutagenesis, we demonstrate that DAF-12 is required for the requisite developmental arrest and the ligand-dependent reactivation of infectious S. stercoralis infective third-stage larvae, and that these effects require the DIP-1 coactivator. These studies reveal the existence of a distinct nuclear receptor/coactivator signaling pathway that governs parasite development.

Original languageEnglish (US)
Article numbere2021864118
JournalProceedings of the National Academy of Sciences of the United States of America
Volume118
Issue number8
DOIs
StatePublished - Feb 23 2021

Keywords

  • Coactivator
  • DAF-12
  • Nematode parasite
  • Nuclear receptor
  • Strongyloides stercoralis

ASJC Scopus subject areas

  • General

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