Journal of Neural Transmission

, Volume 117, Issue 5, pp 599–604 | Cite as

Parkinson’s disease-associated DJ-1 modulates innate immunity signaling in Caenorhabditis elegans

  • Elena M. Cornejo Castro
  • Jens Waak
  • Stephanie S. Weber
  • Fabienne C. Fiesel
  • Philipp Oberhettinger
  • Monika Schütz
  • Ingo B. Autenrieth
  • Wolfdieter Springer
  • Philipp J. Kahle
Basic Neurosciences, Genetics and Immunology - Short Communication

Abstract

DJ-1 is a neuroprotective gene mutated in recessive Parkinson’s disease (PD). In addition to direct protective functions in neurons, DJ-1 regulates neuroinflammatory signaling in primary mouse brain astrocytes. To assess the influence of DJ-1 on innate immunity signaling in vivo, we have generated djr-1 knockout Caenorhabditis elegans. When grown on pathogenic gram-negative bacteria, djr-1−/− worms showed stronger phosphorylation of p38 mitogen-activated protein kinase (PMK-1) and hyper-induction of PMK-1 target genes. Thus, PD-associated DJ-1 contributes to regulation of innate immunity.

Keywords

Caenorhabditis elegans DJ-1 Innate immunity Parkinson’s disease p38MAPK pathway 

Supplementary material

702_2010_397_MOESM1_ESM.doc (52 kb)
Supplementary Table S1 (DOC 52 kb)

References

  1. Bandopadhyay R, Kingsbury AE, Cookson MR, Reid AR, Evans IM, Hope AD, Pittman AM, Lashley T, Canet-Avilés R, Miller DW, McLendon C, Strand C, Leonard AJ, Abou-Sleiman PM, Healy DG, Ariga H, Wood NW, de Silva R, Revesz T, Hardy JA, Lees AJ (2004) The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson’s disease. Brain 127:420–430CrossRefPubMedGoogle Scholar
  2. Bandyopadhyay S, Cookson MR (2004) Evolutionary and functional relationships within the DJ1 superfamily. BMC Evol Biol 4:6CrossRefPubMedGoogle Scholar
  3. Bolz DD, Tenor JL, Aballay A (2010) A conserved PMK-1/p38 MAPK is required in C. elegans tissue-specific immune response to Y. pestis infection. J Biol Chem (in press)Google Scholar
  4. Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MCJ, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P (2003) Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science 299:256–259CrossRefPubMedGoogle Scholar
  5. Bork P, Beckmann G (1993) The CUB domain. J Mol Biol 231:539–545CrossRefPubMedGoogle Scholar
  6. Canet-Avilés RM, Wilson MA, Miller DW, Ahmad R, McLendon C, Bandyopadhyay S, Baptista MJ, Ringe D, Petsko GA, Cookson MR (2004) The Parkinson’s disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization. Proc Natl Acad Sci USA 101:9103–9108CrossRefPubMedGoogle Scholar
  7. Clements CM, McNally RS, Conti BJ, Mak TW, Ting JP-Y (2006) DJ-1, a cancer- and Parkinson’s disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc Natl Acad Sci USA 103:15091–15096CrossRefPubMedGoogle Scholar
  8. Fan J, Ren H, Jia N, Fei E, Zhou T, Jiang P, Wu M, Wang G (2008) DJ-1 decreases Bax expression through repressing p53 transcriptional activity. J Biol Chem 283:4022–4030CrossRefPubMedGoogle Scholar
  9. Görner K, Holtorf E, Waak J, Pham T-T, Vogt-Weisenhorn DM, Wurst W, Haass C, Kahle PJ (2007) Structural determinants of the C-terminal helix-kink-helix motif essential for protein stability and survival promoting activity of DJ-1. J Biol Chem 282:13680–13691CrossRefPubMedGoogle Scholar
  10. Junn E, Taniguchi H, Jeong BS, Zhao X, Ichijo H, Mouradian MM (2005) Interaction of DJ-1 with Daxx inhibits apoptosis signal-regulating kinase 1 activity and cell death. Proc Natl Acad Sci USA 102:9691–9696CrossRefPubMedGoogle Scholar
  11. Kahle PJ, Waak J, Gasser T (2009) DJ-1 and prevention of oxidative stress in Parkinson’s disease and other age-related disorders. Free Radic Biol Med 47:1354–1361CrossRefPubMedGoogle Scholar
  12. Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, Tanaka-Hino M, Hisamoto N, Matsumoto K, Tan M-W, Ausubel FM (2002) A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297:623–626CrossRefPubMedGoogle Scholar
  13. McGreal EP, Martinez-Pomares L, Gordon S (2004) Divergent roles for C-type lectins expressed by cells of the innate immune system. Mol Immunol 41:1109–1121CrossRefPubMedGoogle Scholar
  14. Mullett SJ, Hamilton RL, Hinkle DA (2009) DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age. Neuropathology 29:125–131CrossRefPubMedGoogle Scholar
  15. Neumann M, Müller V, Görner K, Kretzschmar HA, Haass C, Kahle PJ (2004) Pathological properties of the Parkinson’s disease-associated protein DJ-1 in α-synucleinopathies and tauopathies: relevance for multiple system atrophy and Pick’s disease. Acta Neuropathol 107:489–496CrossRefPubMedGoogle Scholar
  16. Takeda K, Noguchi T, Naguro I, Ichijo H (2008) Apoptosis signal-regulating kinase 1 in stress and immune response. Annu Rev Pharmacol Toxicol 48:199–225CrossRefPubMedGoogle Scholar
  17. Troemel ER, Chu SW, Reinke V, Lee SS, Ausubel FM, Kim DH (2006) p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2:e183CrossRefPubMedGoogle Scholar
  18. Ved R, Saha S, Westlund B, Perier C, Burnam L, Sluder A, Hoener M, Rodrigues CMP, Alfonso A, Steer C, Liu L, Przedborski S, Wolozin B (2005) Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of α-synuclein, parkin, and DJ-1 in Caenorhabditis elegans. J Biol Chem 280:42655–42668CrossRefPubMedGoogle Scholar
  19. Waak J, Weber SS, Görner K, Schall C, Ichijo H, Stehle T, Kahle PJ (2009a) Oxidizable residues mediating protein stability and cytoprotective interaction of DJ-1 with apoptosis signal-regulating kinase 1. J Biol Chem 284:14245–14257CrossRefPubMedGoogle Scholar
  20. Waak J, Weber SS, Waldenmaier A, Görner K, Alunni-Fabbroni M, Schell H, Vogt-Weisenhorn D, Pham TT, Reumers V, Baekelandt V, Wurst W, Kahle PJ (2009b) Regulation of astrocyte inflammatory responses by the Parkinson’s disease-associated gene DJ-1. FASEB J 23:2478–2489CrossRefPubMedGoogle Scholar
  21. Xu J, Zhong N, Wang H, Elias JE, Kim CY, Woldman I, Pifl C, Gygi SP, Geula C, Yankner BA (2005) The Parkinson’s disease-associated DJ-1 protein is a transcriptional co-activator that protects against neuronal apoptosis. Hum Mol Genet 14:1231–1241CrossRefPubMedGoogle Scholar
  22. Yang Y, Gehrke S, Haque ME, Imai Y, Kosek J, Yang L, Beal MF, Nishimura I, Wakamatsu K, Ito S, Takahashi R, Lu B (2005) Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase/Akt signaling. Proc Natl Acad Sci USA 102:13670–13675CrossRefPubMedGoogle Scholar
  23. Zhang X, Zhang Y (2009) Neural-immune communication in Caenorhabditis elegans. Cell Host Microbe 5:425–429CrossRefPubMedGoogle Scholar
  24. Zhou W, Freed CR (2005) DJ-1 up-regulates glutathione synthesis during oxidative stress and inhibits A53T alpha-synuclein toxicity. J Biol Chem 280:43150–43158CrossRefPubMedGoogle Scholar
  25. Zucchelli S, Vilotti S, Calligaris R, Lavina ZS, Biagioli M, Foti R, De Maso L, Pinto M, Gorza M, Speretta E, Casseler C, Tell G, Del Sal G, Gustincich S (2009) Aggresome-forming TTRAP mediates pro-apoptotic properties of Parkinson’s disease-associated DJ-1 missense mutations. Cell Death Differ 16:428–438CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Elena M. Cornejo Castro
    • 1
  • Jens Waak
    • 1
    • 2
  • Stephanie S. Weber
    • 1
  • Fabienne C. Fiesel
    • 1
  • Philipp Oberhettinger
    • 3
  • Monika Schütz
    • 3
  • Ingo B. Autenrieth
    • 3
  • Wolfdieter Springer
    • 1
  • Philipp J. Kahle
    • 1
  1. 1.Laboratory of Functional Neurogenetics, Department of NeurodegenerationHertie Institute for Clinical Brain Research, German Center for Neurodegenerative Diseases, University of TübingenTübingenGermany
  2. 2.Nexigen GmbHBonnGermany
  3. 3.Institute of Medical Microbiology and HygieneUniversity Clinics TübingenTübingenGermany

Personalised recommendations