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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