1887

Abstract

Although arsenic is notoriously poisonous to life, its utilization in therapeutics brings many benefits to human health, so it is therefore essential to discover the molecular mechanisms underlying arsenic stress responses in eukaryotic cells. Aiming to determine the contribution of Ca signalling pathways to arsenic stress responses, we took advantage of the use of as a model organism. Here we show that Ca enhances the tolerance of the wild-type and arsenic-sensitive strains to arsenic stress in a Crz1-dependent manner, thus providing the first evidence that Ca signalling cascades are involved in arsenic stress responses. Moreover, our results indicate that arsenic shock elicits a cytosolic Ca burst in these strains, without the addition of exogenous Ca sources, strongly supporting the notion that Ca homeostasis is disrupted by arsenic stress. In response to an arsenite-induced increase of Ca in the cytosol, Crz1 is dephosphorylated and translocated to the nucleus, and stimulates CDRE-driven expression of the reporter gene in a Cnb1-dependent manner. The activation of Crz1 by arsenite culminates in the induction of the endogenous genes and . Taken together, these data establish that activation of Ca signalling pathways and the downstream activation of the Crz1 transcription factor contribute to arsenic tolerance in the eukaryotic model organism .

Loading

Article metrics loading...

/content/journal/micro/10.1099/mic.0.059170-0
2012-09-01
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/micro/158/9/2293.html?itemId=/content/journal/micro/10.1099/mic.0.059170-0&mimeType=html&fmt=ahah

References

  1. Abelovska L., Bujdos M., Kubova J., Petrezselyova S., Nosek J., Tomaska L.. ( 2007;). Comparison of element levels in minimal and complex yeast media. . Can J Microbiol 53:, 533–535. [CrossRef][PubMed]
    [Google Scholar]
  2. Araki Y., Wu H., Kitagaki H., Akao T., Takagi H., Shimoi H.. ( 2009;). Ethanol stress stimulates the Ca2+-mediated calcineurin/Crz1 pathway in Saccharomyces cerevisiae. . J Biosci Bioeng 107:, 1–6. [CrossRef][PubMed]
    [Google Scholar]
  3. Ausubel F. M., Brent R., Kingston R. E., Moore D. D., Seidman J. G., Smith J. A., Struhl K.. (editors) ( 1995;). Current Protocols in Molecular Biology. New York:: Greene Publishing Associates & Wiley-Interscience;.
    [Google Scholar]
  4. Batiza A. F., Schulz T., Masson P. H.. ( 1996;). Yeast respond to hypotonic shock with a calcium pulse. . J Biol Chem 271:, 23357–23362. [CrossRef][PubMed]
    [Google Scholar]
  5. Binet F., Chiasson S., Girard D.. ( 2010;). Arsenic trioxide induces endoplasmic reticulum stress-related events in neutrophils. . Int Immunopharmacol 10:, 508–512. [CrossRef][PubMed]
    [Google Scholar]
  6. Cyert M. S.. ( 2001;). Genetic analysis of calmodulin and its targets in Saccharomyces cerevisiae. . Annu Rev Genet 35:, 647–672. [CrossRef][PubMed]
    [Google Scholar]
  7. Cyert M. S.. ( 2003;). Calcineurin signaling in Saccharomyces cerevisiae: how yeast go crazy in response to stress. . Biochem Biophys Res Commun 311:, 1143–1150. [CrossRef][PubMed]
    [Google Scholar]
  8. Cyert M. S., Thorner J.. ( 1992;). Regulatory subunit (CNB1 gene product) of yeast Ca2+/calmodulin-dependent phosphoprotein phosphatases is required for adaptation to pheromone. . Mol Cell Biol 12:, 3460–3469.[PubMed]
    [Google Scholar]
  9. Cyert M. S., Kunisawa R., Kaim D., Thorner J.. ( 1991;). Yeast has homologs (CNA1 and CNA2 gene products) of mammalian calcineurin, a calmodulin-regulated phosphoprotein phosphatase. . Proc Natl Acad Sci U S A 88:, 7376–7380. [CrossRef][PubMed]
    [Google Scholar]
  10. Denis V., Cyert M. S.. ( 2002;). Internal Ca2+ release in yeast is triggered by hypertonic shock and mediated by a TRP channel homologue. . J Cell Biol 156:, 29–34. [CrossRef][PubMed]
    [Google Scholar]
  11. Güldener U., Heck S., Fielder T., Beinhauer J., Hegemann J. H.. ( 1996;). A new efficient gene disruption cassette for repeated use in budding yeast. . Nucleic Acids Res 24:, 2519–2524. [CrossRef][PubMed]
    [Google Scholar]
  12. Haugen A. C., Kelley R., Collins J. B., Tucker C. J., Deng C., Afshari C. A., Brown J. M., Ideker T., Van Houten B.. ( 2004;). Integrating phenotypic and expression profiles to map arsenic-response networks. . Genome Biol 5:, R95. [CrossRef][PubMed]
    [Google Scholar]
  13. Heath V. L., Shaw S. L., Roy S., Cyert M. S.. ( 2004;). Hph1p and Hph2p, novel components of calcineurin-mediated stress responses in Saccharomyces cerevisiae. . Eukaryot Cell 3:, 695–704. [CrossRef][PubMed]
    [Google Scholar]
  14. Kanzaki M., Nagasawa M., Kojima I., Sato C., Naruse K., Sokabe M., Iida H.. ( 1999;). Molecular identification of a eukaryotic, stretch-activated nonselective cation channel. . Science 285:, 882–886. [CrossRef][PubMed]
    [Google Scholar]
  15. Lallemand-Breitenbach V., Zhu J., Chen Z., de Thé H.. ( 2012;). Curing APL through PML/RARA degradation by As2O3. . Trends Mol Med 18:, 36–42. [CrossRef][PubMed]
    [Google Scholar]
  16. Li X., Qian J., Wang C., Zheng K., Ye L., Fu Y., Han N., Bian H., Pan J.. & other authors ( 2011;). Regulating cytoplasmic calcium homeostasis can reduce aluminum toxicity in yeast. . PLoS ONE 6:, e21148. [CrossRef][PubMed]
    [Google Scholar]
  17. Matheos D. P., Kingsbury T. J., Ahsan U. S., Cunningham K. W.. ( 1997;). Tcn1p/Crz1p, a calcineurin-dependent transcription factor that differentially regulates gene expression in Saccharomyces cerevisiae. . Genes Dev 11:, 3445–3458. [CrossRef][PubMed]
    [Google Scholar]
  18. Matsumoto T. K., Ellsmore A. J., Cessna S. G., Low P. S., Pardo J. M., Bressan R. A., Hasegawa P. M.. ( 2002;). An osmotically induced cytosolic Ca2+ transient activates calcineurin signaling to mediate ion homeostasis and salt tolerance of Saccharomyces cerevisiae. . J Biol Chem 277:, 33075–33080. [CrossRef][PubMed]
    [Google Scholar]
  19. Menezes R. A., Amaral C., Delaunay A., Toledano M., Rodrigues-Pousada C.. ( 2004;). Yap8p activation in Saccharomyces cerevisiae under arsenic conditions. . FEBS Lett 566:, 141–146. [CrossRef][PubMed]
    [Google Scholar]
  20. Menezes R. A., Amaral C., Batista-Nascimento L., Santos C., Ferreira R. B., Devaux F., Eleutherio E. C., Rodrigues-Pousada C.. ( 2008;). Contribution of Yap1 towards Saccharomyces cerevisiae adaptation to arsenic-mediated oxidative stress. . Biochem J 414:, 301–311. [CrossRef][PubMed]
    [Google Scholar]
  21. Miller J. H.. ( 1972;). Experiments in Molecular Genetics. Cold Spring Harbor, NY:: Cold Spring Harbor Laboratory;.
    [Google Scholar]
  22. Palmer C. P., Zhou X. L., Lin J., Loukin S. H., Kung C., Saimi Y.. ( 2001;). A TRP homolog in Saccharomyces cerevisiae forms an intracellular Ca2+-permeable channel in the yeast vacuolar membrane. . Proc Natl Acad Sci U S A 98:, 7801–7805. [CrossRef][PubMed]
    [Google Scholar]
  23. Peiter E., Fischer M., Sidaway K., Roberts S. K., Sanders D.. ( 2005;). The Saccharomyces cerevisiae Ca2+ channel Cch1pMid1p is essential for tolerance to cold stress and iron toxicity. . FEBS Lett 579:, 5697–5703. [CrossRef][PubMed]
    [Google Scholar]
  24. Popa C. V., Dumitru I., Ruta L. L., Danet A. F., Farcasanu I. C.. ( 2010;). Exogenous oxidative stress induces Ca2+ release in the yeast Saccharomyces cerevisiae. . FEBS J 277:, 4027–4038. [CrossRef][PubMed]
    [Google Scholar]
  25. Puig S., Askeland E., Thiele D. J.. ( 2005;). Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation. . Cell 120:, 99–110. [CrossRef][PubMed]
    [Google Scholar]
  26. Rodrigues-Pousada C., Menezes R. A., Pimentel C.. ( 2010;). The Yap family and its role in stress response. . Yeast 27:, 245–258. [CrossRef][PubMed]
    [Google Scholar]
  27. Sánchez-Piris M., Posas F., Alemany V., Winge I., Hidalgo E., Bachs O., Aligue R.. ( 2002;). The serine/threonine kinase Cmk2 is required for oxidative stress response in fission yeast. . J Biol Chem 277:, 17722–17727. [CrossRef][PubMed]
    [Google Scholar]
  28. Serrano M., Real G., Santos J., Carneiro J., Moran C. P. Jr, Henriques A. O.. ( 2011;). A negative feedback loop that limits the ectopic activation of a cell type-specific sporulation sigma factor of Bacillus subtilis. . PLoS Genet 7:, e1002220. [CrossRef][PubMed]
    [Google Scholar]
  29. Stathopoulos A. M., Cyert M. S.. ( 1997;). Calcineurin acts through the CRZ1/TCN1-encoded transcription factor to regulate gene expression in yeast. . Genes Dev 11:, 3432–3444. [CrossRef][PubMed]
    [Google Scholar]
  30. Stathopoulos-Gerontides A., Guo J. J., Cyert M. S.. ( 1999;). Yeast calcineurin regulates nuclear localization of the Crz1p transcription factor through dephosphorylation. . Genes Dev 13:, 798–803. [CrossRef][PubMed]
    [Google Scholar]
  31. Thorsen M., Lagniel G., Kristiansson E., Junot C., Nerman O., Labarre J., Tamás M. J.. ( 2007;). Quantitative transcriptome, proteome, and sulfur metabolite profiling of the Saccharomyces cerevisiae response to arsenite. . Physiol Genomics 30:, 35–43. [CrossRef][PubMed]
    [Google Scholar]
  32. Thorsen M., Perrone G. G., Kristiansson E., Traini M., Ye T., Dawes I. W., Nerman O., Tamás M. J.. ( 2009;). Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae. . BMC Genomics 10:, 105. [CrossRef][PubMed]
    [Google Scholar]
  33. Tseng C. H.. ( 2007;). Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective. . J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 25:, 1–22. [CrossRef][PubMed]
    [Google Scholar]
  34. Viladevall L., Serrano R., Ruiz A., Domenech G., Giraldo J., Barceló A., Ariño J.. ( 2004;). Characterization of the calcium-mediated response to alkaline stress in Saccharomyces cerevisiae. . J Biol Chem 279:, 43614–43624. [CrossRef][PubMed]
    [Google Scholar]
  35. Yoshimoto H., Saltsman K., Gasch A. P., Li H. X., Ogawa N., Botstein D., Brown P. O., Cyert M. S.. ( 2002;). Genome-wide analysis of gene expression regulated by the calcineurin/Crz1p signaling pathway in Saccharomyces cerevisiae. . J Biol Chem 277:, 31079–31088. [CrossRef][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/mic.0.059170-0
Loading
/content/journal/micro/10.1099/mic.0.059170-0
Loading

Data & Media loading...

Supplements

Supplementary data 

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error