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Regulation of cell polarity by control of Sut1-mediated gene expression via the Cdc42 effectors Ste20, Cla4 and Skm1

Applicant Professor Dr. Stefan Rose-John, since 4/2010
Subject Area Cell Biology
Term from 2009 to 2013
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 95085825
 
Final Report Year 2013

Final Report Abstract

Sut1 is a transcriptional regulator of the Zn(II)2Cys6 family in the budding yeast Saccharomyces cerevisiae. The only function that has been attributed to Sut1 is sterol uptake under anaerobic conditions. In this project we characterized novel functions of Sut1. SUT1 over-expression blocks filamentous growth, a response to nutrient limitation, in both haploid and diploid cells. This inhibition by Sut1 is independent of its function in sterol uptake. Sut1 down-regulates the expression of GAT2, HAP4, MGA1, MSN4, NCE102, PRR2, RHO3 and RHO5. Several of these Sut1 targets (GAT2, HAP4, MGA1, RHO3 and RHO5) are essential for filamentation in haploids and/or diploids. Furthermore, the expression of the Sut1 targets genes with the exception of MGA1 is induced during filamentous growth. We have also shown that SUT1 expression is auto-regulated and inhibited by Ste12, a key transcriptional regulator of filamentation. We propose that Sut1 partially represses the expression of GAT2, HAP4, MGA1, MSN4, NCE102, PRR2, RHO3 and RHO5 when nutrients are plentiful. Filamentation-inducing conditions relieve this repression by Sut1 and the increased expression of Sut1 targets triggers filamentous growth. We have also shown that Sut1 and Sut2 are involved in mating. Cells that lack both SUT1 and SUT2 were defective in mating. The expression of the genes NCE102 and PRR2 was increased in this double mutant. Consistent with these data, overexpression of either SUT1 or SUT2 led to lower expression of NCE102 and PRR2. Furthermore, expression levels of NCE102 and PRR2 decreased in response to pheromone. Prr2 has been identified as a mating inhibitor before. Here we show that overexpression of NCE102 also reduced mating. Our results suggest that Sut1 and Sut2 positively regulate mating by repressing the expression of the mating inhibitors NCE102 and PRR2 in response to pheromone. Taken together, it seems that Sut1 regulates several differentiation pathways in budding yeast. For filamentation Sut1-mediated repression is relieved whereas for mating this repression increases.

Publications

  • (2009). The Cdc42 effectors Ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway. Mol. Biol. Cell 20:4826-4837
    Lin M, Unden H, Jacquier N, Schneiter R, Just U and Höfken T
  • (2013). The zinc cluster protein Sut1 contributes to filamentation in Saccharomyces cerevisiae. Eukaryot. Cell 12:244-253
    Foster HA, Cui M, Naveenathayalan A, Unden H, Schwanbeck R and Höfken T
    (See online at https://doi.org/10.1128/EC.00214-12)
 
 

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