title: Ypt protein prenylation depends on the interplay among levels of Rab escort protein and geranylgeranyl diphosphate in yeast cells.
abstract: Farnesyl diphosphate (FPP), an intermediate of the sterol biosynthetic pathway, is used by farnesyl transferase to farnesylate, among others, the Ras proteins, and by geranylgeranyl diphosphate synthase to produce geranylgeranyl diphosphate (GGPP). GGPP is then transferred by geranylgeranyl transferase II (GGTase II) to Rab/Ypt members of the Ras superfamily known to be required at all stages of vesicle transport in both mammals and yeast. Formation of a complex between a Rab/Ypt protein and an accessory protein named the Rab escort protein (REP) is a prerequisite for GGTase II substrate recognition. Little is known about the factors that regulate GGTase II activity in living cells but, based on available data, it seems possible that vesicle transport in higher eukaryotes is regulated by the levels of prenylated Rab/Ypt proteins in the cells. Here we show that the levels of REP play an important role in regulating GGTase II activity in yeast cells if sufficient substrates are present. Moreover, overexpression of REP causes, directly or indirectly, an increased level of Ypt substrates available for prenylation, which in turn leads to the depletion of the GGPP pool in the cell. Overall our data suggest that the levels of REP and the availability of GGPP play a role in regulating Ypt protein prenylation.
authors.affiliation: Vienna Biocenter, Institute of Microbiology and Genetics, University of Vienna, Dr. Bohrgasse 9, A-1030 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Miaczynska
authors.forename: W
authors.initials: W
authors.lastname: Wagner
authors.forename: B E
authors.initials: BE
authors.lastname: Bauer
authors.forename: R J
authors.initials: RJ
authors.lastname: Schweyen
authors.forename: A
authors.initials: A
authors.lastname: Ragnini
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D009154:Mutation; D011106:Polyisoprenyl Phosphates / Q000096:biosynthesis / Q000378:metabolism*; D017368:Protein Prenylation; D029701:Saccharomyces cerevisiae Proteins; D015003:Yeasts; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D011106:Polyisoprenyl Phosphates; D029701:Saccharomyces cerevisiae Proteins; D019883:Alkyl and Aryl Transferases; C060755:YPT1 protein, S cerevisiae; D020691:rab GTP-Binding Proteins; C002963:geranylgeranyl pyrophosphate