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The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans

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Cell Stress and Chaperones Aims and scope

Abstract

The p38 mitogen-activated protein kinase PMK-1 of Caenorhabditis elegans has been associated with heavy metal, oxidative and pathogen stress. Pmk-1 is part of an operon comprising three p38 homologues, with pmk-1 expression suggested to be regulated by the operon promoter. There are contradictory reports about the cellular localization of PMK-1. We were interested to study principles of pmk-1 expression and to analyze the role of PMK-1 under heat stress. Using a translational GFP reporter, we found pmk-1 expression to be driven by a promoter in front of pmk-1. PMK-1 was detected in intestinal cells and neurons, with a cytoplasmic localization at moderate temperature. Increasing temperature above 32 °C, however, induced a nuclear translocation of PMK-1 as well as PMK-1 accumulation near to apical membranes. Testing survival rates revealed 34–35 °C as critical temperature range, where short-term survival severely decreased. Mutants of the PMK-1 pathway (pmk-1Δ, sek-1Δ, mek-1Δ) as well as a mutant of JNK pathway (jnk-1Δ) showed significantly lower survival rates than wild-type or mutants of other pathways (kgb-1Δ, daf-2Δ). Rescue and overexpression experiments verified the negative effects of pmk-1Δ on heat tolerance. Studying gene expression by RNA-seq and semi-quantitative reverse transcriptase polymerase chain reaction revealed positive effects of the PMK-1 pathway on the expression of genes for chaperones, protein biosynthesis, protein degradation, and other functional categories. Thus, the PMK-1 pathway is involved in the heat stress responses of C. elegans, possibly by a PMK-1-mediated activation of the transcription factor SKN-1 and/or an indirect or direct PMK-1-dependent activation (hyperphosphorylation) of heat-shock factor 1.

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Acknowledgments

We thank Frank Nunes, Daniel Runde, and Ulrike Gigengack for supporting material and measurements, the Caenorhabditis Genetics Center for providing C. elegans strains, and the Deutsche Forschungsgemeinschaft for financial support (Pa 308/13-1).

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  1. Institute of Zoophysiology, University of Münster, Schlossplatz 8, 48143, Münster, Germany

    Ansgar Mertenskötter, Alex Keshet, Peter Gerke & Rüdiger J. Paul

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  1. Ansgar Mertenskötter
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  2. Alex Keshet
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  4. Rüdiger J. Paul
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Correspondence to Ansgar Mertenskötter.

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Mertenskötter, A., Keshet, A., Gerke, P. et al. The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans. Cell Stress and Chaperones 18, 293–306 (2013). https://doi.org/10.1007/s12192-012-0382-y

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