Role of the fission yeast cell integrity MAPK pathway in response to glucose limitation

Marisa Madrid,Jesús Fernández-Zapata,Teresa Soto,José Cansado,Mariano Gacto,Alejandro Franco,Jero Vicente-Soler,Laura Sánchez-Mir

doi:10.1186/1471-2180-13-34

Abstract

BackgroundGlucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The ability of this yeast to grow in the absence of glucose becomes strongly limited due to lack of enzymes of the glyoxylate cycle that support diauxic growth. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty1 MAPK and transcription factor Atf1, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase. The cell integrity Pmk1 pathway is another MAPK cascade that regulates various processes in fission yeast, including cell wall construction, cytokinesis, and ionic homeostasis. Pmk1 pathway also becomes strongly activated in response to glucose deprivation but its role during glucose exhaustion and ensuing adaptation to respiratory metabolism is currently unknown.ResultsWe found that Pmk1 activation in the absence of glucose takes place only after complete depletion of this carbon source and that such activation is not related to an endogenous oxidative stress. Notably, Pmk1 MAPK activation relies on de novo protein synthesis, is independent on known upstream activators of the pathway like Rho2 GTPase, and involves PKC ortholog Pck2. Also, the Glucose/cAMP pathway is required operative for full activation of the Pmk1 signaling cascade. Mutants lacking Pmk1 displayed a partial growth defect in respiratory media which was not observed in the presence of glucose. This phenotype was accompanied by a decreased and delayed expression of transcription factor Atf1 and target genes fbp1+ and pyp2+. Intriguingly, the kinetics of Sty1 activation in Pmk1-less cells was clearly altered during growth adaptation to non-fermentable carbon sources.ConclusionsUnknown upstream elements mediate Pck2-dependent signal transduction of glucose withdrawal to the cell integrity MAPK pathway. This signaling cascade reinforces the adaptive response of fission yeast to such nutritional stress by enhancing the activity of the SAPK pathway.

Highlights

Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe
Pmk1 activation in response to glucose deprivation We have previously described that glucose exhaustion is one of the multiple physiological insults which activate the Pmk1 mitogen-activated protein kinase (MAPK) signaling pathway in fission yeast [17]
Transfer of exponentially growing cells from rich glucose medium (7% w/v) to osmotically equilibrated medium with glucose concentrations of either 1% or 0.5% did not elicit a significant increase in Pmk1 phosphorylation (Figure 1A), suggesting that full activation of the MAPK cell integrity pathway in S. pombe only takes place after complete depletion of this carbon source

Summary

Introduction

Glucose is a signaling molecule which regulates multiple events in eukaryotic organisms and the most preferred carbon source in the fission yeast Schizosaccharomyces pombe. The stress-activated protein kinase (SAPK) pathway and its effectors, Sty MAPK and transcription factor Atf, play a critical role in the adaptation of fission yeast to grow on alternative non-fermentable carbon sources by inducing the expression of fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6bisphosphatase. Glucose starvation is an environmental stress able to activate the SAPK pathway in S. pombe [11,12], and mutants lacking either Sty or Atf are unable to grow on alternative non-fermentable carbon sources due to failure to induce the fbp1+ gene, coding for the gluconeogenic enzyme fructose-1,6-bisphosphatase [13]. Pka phosphorylates and negatively regulates the activity of Rst, a transcription factor which, together with Atf, is responsible for the induced expression of fbp1+ when glucose is missing [14]

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