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Temporal Quantification of MAPK Induced Expression in Single Yeast Cells
Published on: October 4, 2013
Manganese Stress Tolerance Depends on Yap1 and Stress-Activated MAP Kinases
Inés G de Oya1,2, Elena Jiménez-Gutiérrez3,4, Hélène Gaillard1,2
1Centro Andaluz de Biología Molecular y Medicina Regenerativa, Universidad de Sevilla, Avda. Américo Vespucio s/n, 41092 Sevilla, Spain.
Abstract:
Understanding which intracellular signaling pathways are activated by manganese stress is crucial to decipher how metal overload compromise cellular integrity. Here, we unveil a role for oxidative and cell wall stress signaling in the response to manganese stress in yeast. We find that the oxidative stress transcription factor Yap1 protects cells against manganese toxicity. Conversely, extracellular manganese addition causes a rapid decay in Yap1 protein levels. In addition, manganese stress activates the MAPKs Hog1 and Slt2 (Mpk1) and leads to an up-regulation of the Slt2 downstream transcription factor target Rlm1. Importantly, Yap1 and Slt2 are both required to protect cells from oxidative stress in mutants impaired in manganese detoxification. Under such circumstances, Slt2 activation is enhanced upon Yap1 depletion suggesting an interplay between different stress signaling nodes to optimize cellular stress responses and manganese tolerance.
Insights
Manganese stress impacts yeast cells by activating oxidative and cell wall stress pathways. The transcription factor Yap1 and MAPK Slt2 are key players in protecting yeast against manganese toxicity and related oxidative damage.
Area of Science:
- Cellular biology
- Environmental toxicology
- Yeast genetics
Background:
- Metal overload can compromise cellular integrity through poorly understood signaling pathways.
- Manganese stress is a significant environmental factor affecting cellular function.
Purpose of the Study:
- To investigate the intracellular signaling pathways activated by manganese stress in yeast.
- To elucidate the roles of oxidative and cell wall stress responses in manganese tolerance.
Main Methods:
- Yeast model system utilized.
- Analysis of transcription factor Yap1 protein levels under manganese stress.
- Monitoring of MAPK (Hog1, Slt2) activation.
- Assessment of downstream targets like Rlm1.
- Genetic analysis of Yap1 and Slt2 roles in manganese detoxification mutants.
Main Results:
- Manganese stress activates oxidative and cell wall stress signaling pathways in yeast.
- The transcription factor Yap1 confers protection against manganese toxicity, although its protein levels decrease with manganese exposure.
- MAPKs Hog1 and Slt2 are activated by manganese stress, leading to Rlm1 up-regulation.
- Yap1 and Slt2 are essential for protection against oxidative stress in yeast with impaired manganese detoxification.
- Slt2 activation is enhanced by Yap1 depletion, indicating pathway crosstalk.
Conclusions:
- Manganese stress triggers complex signaling responses involving oxidative and cell wall stress pathways in yeast.
- Yap1 and Slt2 play critical, interconnected roles in cellular defense against manganese toxicity and associated oxidative damage.
- Interplay between different stress signaling nodes optimizes manganese tolerance and cellular integrity.
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