title: Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells.
abstract: Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins (PMPs), and is essential for the formation of functional peroxisomal membranes. Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins. In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least partially farnesylated in vivo. Whether farnesylation of Pex19p plays an essential or merely ancillary role in peroxisome biogenesis is currently not clear. Here, we show that (i) nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of PMPs, (ii) a variant of Pex19p lacking a functional farnesylation motif is able to restore peroxisome biogenesis in Pex19p-deficient cells, and (iii) peroxisome protein import is not affected in yeast and mammalian cells defective in one of the enzymes involved in the farnesylation pathway. Summarized, these observations indicate that the CAAX box-mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in yeast and mammalian cells.
authors.affiliation: Laboratorium voor Farmacologie, Departement Moleculaire Celbiologie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Campus Gasthuisberg (O/N 1), Herestraat 49 bus 601, 3000, Leuven, Belgium.
authors.forename: I M K
authors.initials: IM
authors.lastname: Vastiau
authors.forename: E A
authors.initials: EA
authors.lastname: Anthonio
authors.forename: M
authors.initials: M
authors.lastname: Brams
authors.forename: C
authors.initials: C
authors.lastname: Brees
authors.forename: S G
authors.initials: SG
authors.lastname: Young
authors.forename: S
authors.initials: S
authors.lastname: Van de Velde
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: G P
authors.initials: GP
authors.lastname: Mannaerts
authors.forename: M
authors.initials: M
authors.lastname: Baes
authors.forename: P P
authors.initials: PP
authors.lastname: Van Veldhoven
authors.forename: M
authors.initials: M
authors.lastname: Fransen
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D002461:Cell Line, Transformed; D016384:Consensus Sequence; D006224:Cricetinae; D003412:Cricetulus; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D051379:Mice; D019301:Oleic Acid / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D017368:Protein Prenylation / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D008565:Membrane Proteins; C109779:PEX19 protein, S cerevisiae; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; C087343:PEX19 protein, human; D019301:Oleic Acid; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase