Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeastSaccharomyces cerevisiae


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Abstract

The conserved Rho-type GTPase Cdc42p is a key regulator of signal transduction and polarity in eukaryotic cells. In the yeast Saccharomyces cerevisiae, Cdc42p promotes polarized growth through the p21-activated kinases Ste20p and Cla4p. Previously, we demonstrated that Ste20p forms a complex with Erg4p, Cbr1p and Ncp1p, which all catalyze important steps in sterol biosynthesis. CLA4 interacts genetically with ERG4 and NCP1. Furthermore, Erg4p, Ncp1p and Cbr1p play important roles in cell polarization during vegetative growth, mating and filamentation. As Ste20p and Cla4p are involved in these processes it seems likely that sterol biosynthetic enzymes and p21-activated kinases act in related pathways. Here, we demonstrate that the deletion of either STE20 or CLA4 results in increased levels of sterols. In addition, higher concentrations of steryl esters, the storage form of sterols, were observed in cla4Δ cells. CLA4 expression from a multicopy plasmid reduces enzyme activity of Are2p, the major steryl ester synthase, under aerobic conditions. Altogether, our data suggest that Ste20p and Cla4p may function as negative modulators of sterol biosynthesis. Moreover, Cla4p has a negative effect on steryl ester formation. As sterol homeostasis is crucial for cell polarization, Ste20p and Cla4p may regulate cell polarity in part through the modulation of sterol homeostasis.Structured digital abstractMINT-7291456: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with CBR1 (uniprotkb:P38626) by ubiquitin reconstruction (MI:0112)MINT-7291480: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with BEM1 (uniprotkb:P29366) by ubiquitin reconstruction (MI:0112)MINT-7291468: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with NCP1 (uniprotkb:P16603) by ubiquitin reconstruction (MI:0112)MINT-7291441: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with ERG4 (uniprotkb:P25340) by ubiquitin reconstruction (MI:0112)MINT-7291492: CLA4 (uniprotkb:P48562) physically interacts (MI:0915) with BEM1 (uniprotkb:P29366) by ubiquitin reconstruction (MI:0112)MINT-7291412: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with ARE1 (uniprotkb:P25628) by pull down (MI:0096)MINT-7291424: STE20 (uniprotkb:Q03497) physically interacts (MI:0915) with ARE2 (uniprotkb:P53629) by pull down (MI:0096)

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