title: The p38 MAPK PMK-1 shows heat-induced nuclear translocation, supports chaperone expression, and affects the heat tolerance of Caenorhabditis elegans.
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.
authors.affiliation: Institute of Zoophysiology, University of Münster, Schlossplatz 8, 48143, Münster, Germany. a.mertenskoetter@uni-muenster.de
authors.forename: Ansgar
authors.initials: A
authors.lastname: Mertenskötter
authors.forename: Alex
authors.initials: A
authors.lastname: Keshet
authors.forename: Peter
authors.initials: P
authors.lastname: Gerke
authors.forename: Rüdiger J
authors.initials: RJ
authors.lastname: Paul
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000201:enzymology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006358:Hot Temperature; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013312:Stress, Physiological; D016019:Survival Analysis; D013997:Time Factors; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases