title: Arsenic stress elicits cytosolic Ca(2+) bursts and Crz1 activation in Saccharomyces cerevisiae.
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(2+) signalling pathways to arsenic stress responses, we took advantage of the use of Saccharomyces cerevisiae as a model organism. Here we show that Ca(2+) enhances the tolerance of the wild-type and arsenic-sensitive yap1 strains to arsenic stress in a Crz1-dependent manner, thus providing the first evidence that Ca(2+) signalling cascades are involved in arsenic stress responses. Moreover, our results indicate that arsenic shock elicits a cytosolic Ca(2+) burst in these strains, without the addition of exogenous Ca(2+) sources, strongly supporting the notion that Ca(2+) homeostasis is disrupted by arsenic stress. In response to an arsenite-induced increase of Ca(2+) in the cytosol, Crz1 is dephosphorylated and translocated to the nucleus, and stimulates CDRE-driven expression of the lacZ reporter gene in a Cnb1-dependent manner. The activation of Crz1 by arsenite culminates in the induction of the endogenous genes PMR1, PMC1 and GSC2. Taken together, these data establish that activation of Ca(2+) signalling pathways and the downstream activation of the Crz1 transcription factor contribute to arsenic tolerance in the eukaryotic model organism S. cerevisiae.
authors: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Rita T
authors: RT
authors: Ferreira
authors: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Ana R Courelas
authors: ARC
authors: Silva
authors: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Catarina
authors: C
authors: Pimentel
authors: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Liliana
authors: L
authors: Batista-Nascimento
authors: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Claudina
authors: C
authors: Rodrigues-Pousada
authors: Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.
authors: Regina A
authors: RA
authors: Menezes
mesh_terms: D001151:Arsenic / Q000633:toxicity*; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000096:biosynthesis*; D015533:Transcriptional Activation
chemical_list: C109868:CRZ1 protein, S cerevisiae; D002413:Cations, Divalent; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D001151:Arsenic; D002118:Calcium