tailieunhanh - Báo cáo khoa học: Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeast Saccharomyces cerevisiae

The conserved Rho-type GTPase Cdc42p is a key regulator of signal trans-duction and polarity in eukaryotic cells. In the yeastSaccharomyces cerevi-siae, Cdc42p promotes polarized growth through the p21-activated kinases Ste20p and Cla4p. Previously, we demonstrated that Ste20p forms a com-plex with Erg4p, Cbr1p and Ncp1p, which all catalyze important steps in sterol biosynthesis. | ỊFEBS Journal Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeast Saccharomyces cerevisiae Meng Lin1 Karlheinz Grillitsch2 Gunther Daum2 Ursula Just1 and Thomas Hofken1 1 Institute of Biochemistry Christian Albrecht University Kiel Germany 2 Institute of Biochemistry Graz University of Technology Austria Keywords cell polarity p21-activated kinase sterol sterylester yeast Correspondence T. Hofken Institute of Biochemistry Christian Albrecht University Kiel Olshausenstrasse 40 24098 Kiel Germany Fax 49 431 8802609 Tel. 49 431 8801660 E-mail thoefken@ These authors contributed equally to this work Received 2 September 2009 revised 29 September 2009 accepted 12 October 2009 doi The conserved Rho-type GTPase Cdc42p is a key regulator of signal transduction and polarity in eukaryotic cells. In the yeast Saccharomyces cerevi-siae 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 cla4D 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 .