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Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells
Authors:I. M. K. Vastiau  E. A. Anthonio  M. Brams  C. Brees  S. G. Young  S. Van de Velde  R. J. A. Wanders  G. P. Mannaerts  M. Baes  P. P. Van Veldhoven  M. Fransen
Affiliation:(1) Laboratorium voor Farmacologie, Departement Moleculaire Celbiologie, Faculteit Geneeskunde, Katholieke Universiteit Leuven, Campus Gasthuisberg (O/N 1), Herestraat 49 bus 601, 3000 Leuven, Belgium;(2) Department of Medicine, Division of Cardiology, University of California, Los Angeles, California, USA;(3) Laboratorium voor Moleculaire Celbiologie, Departement Biologie, Faculteit Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium;(4) Departement Moleculaire Microbiologie, Vlaams Interuniversitair Instituut voor Biotechnologie, Leuven, Belgium;(5) Laboratorium Genetisch Metabole Ziekten, Departement voor Pediatrie, Academisch Medisch Centrum,Universiteit van Amsterdam, Amsterdam, The Netherlands;(6) Laboratorium voor Klinische Chemie, Faculteit Farmaceutische Wetenschappen, Katholieke Universiteit Leuven, Leuven, Belgium
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. Received 10 March 2006; received after revision 28 April 2006; accepted 30 May 2006
Keywords:Peroxisomes  biogenesis  peroxins  protein import  Pex19p  farnesylation
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