Hsp90-downregulation influences the heat-shock response, innate immune response and onset of oocyte development in nematodes

PLoS One. 2017 Oct 27;12(10):e0186386. doi: 10.1371/journal.pone.0186386. eCollection 2017.

Abstract

Hsp90 is a molecular chaperone involved in the regulation and maturation of kinases and transcription factors. In Caenorhabditis elegans, it contributes to the development of fertility, maintenance of muscle structure, the regulation of heat-shock response and dauer state. To understand the consequences of Hsp90-depletion, we studied Hsp90 RNAi-treated nematodes by DNA microarrays and mass spectrometry. We find that upon development of phenotypes the levels of chaperones and Hsp90 cofactors are increased, while specific proteins related to the innate immune response are depleted. In microarrays, we further find many differentially expressed genes related to gonad and larval development. These genes form an expression cluster that is regulated independently from the immune response implying separate pathways of Hsp90-involvement. Using fluorescent reporter strains for the differentially expressed immune response genes skr-5, dod-24 and clec-60 we observe that their activity in intestinal tissues is influenced by Hsp90-depletion. Instead, effects on the development are evident in both gonad arms. After Hsp90-depletion, changes can be observed in early embryos and adults containing fluorescence-tagged versions of SEPA-1, CAV-1 or PUD-1, all of which are downregulated after Hsp90-depletion. Our observations identify molecular events for Hsp90-RNAi induced phenotypes during development and immune responses, which may help to separately investigate independent Hsp90-influenced processes that are relevant during the nematode's life and development.

MeSH terms

  • Animals
  • Down-Regulation*
  • Gene Expression
  • Gene Regulatory Networks
  • HSP90 Heat-Shock Proteins / metabolism*
  • Heat-Shock Response*
  • Immunity, Innate*
  • Lectins / metabolism
  • Nematoda / cytology
  • Nematoda / immunology*
  • Nematoda / metabolism*
  • Oocytes / cytology*
  • Transcription, Genetic

Substances

  • HSP90 Heat-Shock Proteins
  • Lectins

Grant support

The work was supported by P.U.R.E. (Protein Unit for Research in Europe, funded by the German federal state North Rhine-Westphalia). Klaus Richter is funded by the research grant DFG grant RI1873/1-3. This work was supported by the German Research Foundation (DFG) and the Technical University of Munich within the funding programme Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.