title: Modulation of sterol homeostasis by the Cdc42p effectors  Cla4p and Ste20p in the yeast Saccharomyces cerevisiae.
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 cla4Delta 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.
authors.affiliation: Institute of Biochemistry, Christian Albrecht University, Kiel, Germany.
authors.forename: Meng
authors.initials: M
authors.lastname: Lin
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Grillitsch
authors.forename: Günther
authors.initials: G
authors.lastname: Daum
authors.forename: Ursula
authors.initials: U
authors.lastname: Just
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfken
mesh_terms: D016764:Cell Polarity / Q000187:drug effects; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D020930:MAP Kinase Kinase Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D002785:Sterol O-Acyltransferase / Q000502:physiology; D013261:Sterols / Q000378:metabolism*; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000502:physiology*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; C543386:ARE1 protein, S cerevisiae; C543388:ARE2 protein, S cerevisiae; D002785:Sterol O-Acyltransferase; C095212:CLA4 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D020930:MAP Kinase Kinase Kinases; C078754:STE20 protein, S cerevisiae; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae