Abstract
In this study we analyze the participation of the PKC1-MAPK cell integrity pathway in cellular responses to oxidative stress in Saccharomyces cerevisiae. Evidence is presented demonstrating that only Pkc1 and the upstream elements of the cell integrity pathway are essential for cell survival upon treatment with two oxidizing agents, diamide and hydrogen peroxide. Mtl1 is characterized for the first time as a cell-wall sensor of oxidative stress. We also show that the actin cytoskeleton is a cellular target for oxidative stress. Both diamide and hydrogen peroxide provoke a marked depolarization of the actin cytoskeleton, being Mtl1, Rom2 and Pkc1 functions all required to restore the correct actin organization. Diamide induces the formation of disulfide bonds in newly secreted cell-wall proteins. This mainly provokes structural changes in the cell outer layer, which activate the PKC1-MAPK pathway and hence the protein kinase Slt2. Our results led us to the conclusion that Pkc1 activity is required to overcome the effects of oxidative stress by: (i) enhancing the machinery required to repair the altered cell wall and (ii) restoring actin cytoskeleton polarity by promoting actin cable formation.
Highlights
Cells are constantly exposed to a series of environmental stresses, which are sensed by complex signal transduction pathways that are responsible for cellular damage repair and adaptation responses
Oxidative Stress Provoked by Diamide and Hydrogen Peroxide Activates the Cell Integrity Pathway—Given the role that the cell integrity pathway plays in the response to a wide variety of stresses, we decided to investigate whether this pathway was involved in the oxidative stress response
Pkc1, Rom2, and Mtl1 Are Required for Transmitting the Oxidative Signal to Slt2 and for Cell Viability in Response to Oxidative Stress—Once demonstrated that oxidative stress activates Slt2 mediated by cell wall receptors, we investigated which elements of the cell integrity pathway were involved in this activation
Summary
Cells are constantly exposed to a series of environmental stresses, which are sensed by complex signal transduction pathways that are responsible for cellular damage repair and adaptation responses. In the Saccharomyces cerevisiae, the PKC1-MAPK cell integrity pathway is involved in responses to a wide variety of stresses, including heat-shock [1], hypoosmotic shock [2], nutritional stress [3], and those associated with any other injuries that alter the integrity of the outer layer of cells. These environmental signals are generally sensed by Mid2 [4] and Wsc family [5] cell surface proteins. The function of both Rho and Pkc is necessary for actin to become depolarized following heat stress [12]
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