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J Cell Biol. 1996 October 1; 135(1): 111–121.
PMCID: PMC2121012

Identification of Pex13p a peroxisomal membrane receptor for the PTS1 recognition factor

Abstract

We have identified an S. cerevisiae integral peroxisomal membrane protein of M of 42,705 (Pex13p) that is a component of the peroxisomal protein import apparatus. Pex13p's most striking feature is an src homology 3 (SH3) domain that interacts directly with yeast Pex5p (former Pas10p), the recognition factor for the COOH-terminal tripeptide signal sequence (PTS1), but not with Pex7p (former Pas7p), the recognition factor for the NH2-terminal nonapeptide signal (PTS2) of peroxisomal matrix proteins. Hence, Pex13p serves as peroxisomal membrane receptor for at least one of the two peroxisomal signal recognition factors. Cells deficient in Pex13p are unable to import peroxisomal matrix proteins containing PTS1 and, surprisingly, also those containing PTS2. Pex13p deficient cells retain membranes containing the peroxisomal membrane protein Pex11p (former Pmp27p), consistent with the existence of independent pathways for the integration of peroxisomal membrane proteins and for the translocation of peroxisomal matrix proteins.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Blobel F, Erdmann R. Identification of a yeast peroxisomal member of the family of AMP-binding proteins. Eur J Biochem. 1996 Sep 1;240(2):468–476. [PubMed]
  • Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. [PubMed]
  • Bruschi CV, Comer AR, Howe GA. Specificity of DNA uptake during whole cell transformation of S. cerevisiae. Yeast. 1987 Jun;3(2):131–137. [PubMed]
  • Chevray PM, Nathans D. Protein interaction cloning in yeast: identification of mammalian proteins that react with the leucine zipper of Jun. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):5789–5793. [PubMed]
  • Clark SG, Stern MJ, Horvitz HR. C. elegans cell-signalling gene sem-5 encodes a protein with SH2 and SH3 domains. Nature. 1992 Mar 26;356(6367):340–344. [PubMed]
  • Cohen GB, Ren R, Baltimore D. Modular binding domains in signal transduction proteins. Cell. 1995 Jan 27;80(2):237–248. [PubMed]
  • Dodt G, Braverman N, Wong C, Moser A, Moser HW, Watkins P, Valle D, Gould SJ. Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nat Genet. 1995 Feb;9(2):115–125. [PubMed]
  • Drubin DG, Mulholland J, Zhu ZM, Botstein D. Homology of a yeast actin-binding protein to signal transduction proteins and myosin-I. Nature. 1990 Jan 18;343(6255):288–290. [PubMed]
  • Erdmann R. The peroxisomal targeting signal of 3-oxoacyl-CoA thiolase from Saccharomyces cerevisiae. Yeast. 1994 Jul;10(7):935–944. [PubMed]
  • Erdmann R, Kunau WH. Purification and immunolocalization of the peroxisomal 3-oxoacyl-CoA thiolase from Saccharomyces cerevisiae. Yeast. 1994 Sep;10(9):1173–1182. [PubMed]
  • Erdmann R, Blobel G. Giant peroxisomes in oleic acid-induced Saccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p. J Cell Biol. 1995 Feb;128(4):509–523. [PMC free article] [PubMed]
  • Erdmann R, Veenhuis M, Mertens D, Kunau WH. Isolation of peroxisome-deficient mutants of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5419–5423. [PubMed]
  • Erdmann R, Wiebel FF, Flessau A, Rytka J, Beyer A, Fröhlich KU, Kunau WH. PAS1, a yeast gene required for peroxisome biogenesis, encodes a member of a novel family of putative ATPases. Cell. 1991 Feb 8;64(3):499–510. [PubMed]
  • Evan GI, Lewis GK, Ramsay G, Bishop JM. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985 Dec;5(12):3610–3616. [PMC free article] [PubMed]
  • Fields S, Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. [PubMed]
  • Fransen M, Brees C, Baumgart E, Vanhooren JC, Baes M, Mannaerts GP, Van Veldhoven PP. Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor. J Biol Chem. 1995 Mar 31;270(13):7731–7736. [PubMed]
  • Gilmore R, Blobel G, Walter P. Protein translocation across the endoplasmic reticulum. I. Detection in the microsomal membrane of a receptor for the signal recognition particle. J Cell Biol. 1982 Nov;95(2 Pt 1):463–469. [PMC free article] [PubMed]
  • Glover JR, Andrews DW, Rachubinski RA. Saccharomyces cerevisiae peroxisomal thiolase is imported as a dimer. Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10541–10545. [PubMed]
  • Gould SG, Keller GA, Subramani S. Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase. J Cell Biol. 1987 Dec;105(6 Pt 2):2923–2931. [PMC free article] [PubMed]
  • Hachiya N, Mihara K, Suda K, Horst M, Schatz G, Lithgow T. Reconstitution of the initial steps of mitochondrial protein import. Nature. 1995 Aug 24;376(6542):705–709. [PubMed]
  • Häusler T, Stierhof YD, Wirtz E, Clayton C. Import of a DHFR hybrid protein into glycosomes in vivo is not inhibited by the folate-analogue aminopterin. J Cell Biol. 1996 Feb;132(3):311–324. [PMC free article] [PubMed]
  • Hiltunen JK, Wenzel B, Beyer A, Erdmann R, Fosså A, Kunau WH. Peroxisomal multifunctional beta-oxidation protein of Saccharomyces cerevisiae. Molecular analysis of the fox2 gene and gene product. J Biol Chem. 1992 Apr 5;267(10):6646–6653. [PubMed]
  • Höhfeld J, Veenhuis M, Kunau WH. PAS3, a Saccharomyces cerevisiae gene encoding a peroxisomal integral membrane protein essential for peroxisome biogenesis. J Cell Biol. 1991 Sep;114(6):1167–1178. [PMC free article] [PubMed]
  • Imanaka T, Small GM, Lazarow PB. Translocation of acyl-CoA oxidase into peroxisomes requires ATP hydrolysis but not a membrane potential. J Cell Biol. 1987 Dec;105(6 Pt 2):2915–2922. [PMC free article] [PubMed]
  • Lazarow PB. Genetic approaches to studying peroxisome biogenesis. Trends Cell Biol. 1993 Mar;3(3):89–93. [PubMed]
  • Lazarow PB, Fujiki Y. Biogenesis of peroxisomes. Annu Rev Cell Biol. 1985;1:489–530. [PubMed]
  • Maeda T, Takekawa M, Saito H. Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science. 1995 Jul 28;269(5223):554–558. [PubMed]
  • Marshall PA, Krimkevich YI, Lark RH, Dyer JM, Veenhuis M, Goodman JM. Pmp27 promotes peroxisomal proliferation. J Cell Biol. 1995 Apr;129(2):345–355. [PMC free article] [PubMed]
  • Marzioch M, Erdmann R, Veenhuis M, Kunau WH. PAS7 encodes a novel yeast member of the WD-40 protein family essential for import of 3-oxoacyl-CoA thiolase, a PTS2-containing protein, into peroxisomes. EMBO J. 1994 Oct 17;13(20):4908–4918. [PubMed]
  • McCammon MT, McNew JA, Willy PJ, Goodman JM. An internal region of the peroxisomal membrane protein PMP47 is essential for sorting to peroxisomes. J Cell Biol. 1994 Mar;124(6):915–925. [PMC free article] [PubMed]
  • McNew JA, Goodman JM. An oligomeric protein is imported into peroxisomes in vivo. J Cell Biol. 1994 Dec;127(5):1245–1257. [PMC free article] [PubMed]
  • Moreno de la Garza M, Schultz-Borchard U, Crabb JW, Kunau WH. Peroxisomal beta-oxidation system of Candida tropicalis. Purification of a multifunctional protein possessing enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase and 3-hydroxyacyl-CoA epimerase activities. Eur J Biochem. 1985 Apr 15;148(2):285–291. [PubMed]
  • Moroianu J, Hijikata M, Blobel G, Radu A. Mammalian karyopherin alpha 1 beta and alpha 2 beta heterodimers: alpha 1 or alpha 2 subunit binds nuclear localization signal and beta subunit interacts with peptide repeat-containing nucleoporins. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6532–6536. [PubMed]
  • Osumi T, Tsukamoto T, Hata S, Yokota S, Miura S, Fujiki Y, Hijikata M, Miyazawa S, Hashimoto T. Amino-terminal presequence of the precursor of peroxisomal 3-ketoacyl-CoA thiolase is a cleavable signal peptide for peroxisomal targeting. Biochem Biophys Res Commun. 1991 Dec 31;181(3):947–954. [PubMed]
  • Partanen J, Armstrong E, Bergman M, Mäkelä TP, Hirvonen H, Huebner K, Alitalo K. cyl encodes a putative cytoplasmic tyrosine kinase lacking the conserved tyrosine autophosphorylation site (Y416src). Oncogene. 1991 Nov;6(11):2013–2018. [PubMed]
  • Rachubinski RA, Subramani S. How proteins penetrate peroxisomes. Cell. 1995 Nov 17;83(4):525–528. [PubMed]
  • Ren R, Mayer BJ, Cicchetti P, Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science. 1993 Feb 19;259(5098):1157–1161. [PubMed]
  • Rickles RJ, Botfield MC, Weng Z, Taylor JA, Green OM, Brugge JS, Zoller MJ. Identification of Src, Fyn, Lyn, PI3K and Abl SH3 domain ligands using phage display libraries. EMBO J. 1994 Dec 1;13(23):5598–5604. [PubMed]
  • Rothstein R. Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast. Methods Enzymol. 1991;194:281–301. [PubMed]
  • Rout MP, Kilmartin JV. Components of the yeast spindle and spindle pole body. J Cell Biol. 1990 Nov;111(5 Pt 1):1913–1927. [PMC free article] [PubMed]
  • Santos MJ, Imanaka T, Shio H, Small GM, Lazarow PB. Peroxisomal membrane ghosts in Zellweger syndrome--aberrant organelle assembly. Science. 1988 Mar 25;239(4847):1536–1538. [PubMed]
  • Semba K, Nishizawa M, Miyajima N, Yoshida MC, Sukegawa J, Yamanashi Y, Sasaki M, Yamamoto T, Toyoshima K. yes-related protooncogene, syn, belongs to the protein-tyrosine kinase family. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5459–5463. [PubMed]
  • Sikorski RS, Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. [PubMed]
  • Slawecki ML, Dodt G, Steinberg S, Moser AB, Moser HW, Gould SJ. Identification of three distinct peroxisomal protein import defects in patients with peroxisome biogenesis disorders. J Cell Sci. 1995 May;108(Pt 5):1817–1829. [PubMed]
  • Subramani S. Targeting of proteins into the peroxisomal matrix. J Membr Biol. 1992 Jan;125(2):99–106. [PubMed]
  • Swinkels BW, Gould SJ, Bodnar AG, Rachubinski RA, Subramani S. A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase. EMBO J. 1991 Nov;10(11):3255–3262. [PubMed]
  • Takeya T, Hanafusa H. Structure and sequence of the cellular gene homologous to the RSV src gene and the mechanism for generating the transforming virus. Cell. 1983 Mar;32(3):881–890. [PubMed]
  • van der Klei IJ, Hilbrands RE, Swaving GJ, Waterham HR, Vrieling EG, Titorenko VI, Cregg JM, Harder W, Veenhuis M. The Hansenula polymorpha PER3 gene is essential for the import of PTS1 proteins into the peroxisomal matrix. J Biol Chem. 1995 Jul 21;270(29):17229–17236. [PubMed]
  • Van der Leij I, Franse MM, Elgersma Y, Distel B, Tabak HF. PAS10 is a tetratricopeptide-repeat protein that is essential for the import of most matrix proteins into peroxisomes of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11782–11786. [PubMed]
  • Walton PA, Hill PE, Subramani S. Import of stably folded proteins into peroxisomes. Mol Biol Cell. 1995 Jun;6(6):675–683. [PMC free article] [PubMed]
  • Watanabe M, Blobel G. SecB functions as a cytosolic signal recognition factor for protein export in E. coli. Cell. 1989 Aug 25;58(4):695–705. [PubMed]
  • Wendland M, Subramani S. Cytosol-dependent peroxisomal protein import in a permeabilized cell system. J Cell Biol. 1993 Feb;120(3):675–685. [PMC free article] [PubMed]
  • Wiemer EA, Nuttley WM, Bertolaet BL, Li X, Francke U, Wheelock MJ, Anné UK, Johnson KR, Subramani S. Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. J Cell Biol. 1995 Jul;130(1):51–65. [PMC free article] [PubMed]
  • Yaffe MP, Schatz G. Two nuclear mutations that block mitochondrial protein import in yeast. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4819–4823. [PubMed]
  • Yu H, Chen JK, Feng S, Dalgarno DC, Brauer AW, Schreiber SL. Structural basis for the binding of proline-rich peptides to SH3 domains. Cell. 1994 Mar 11;76(5):933–945. [PubMed]
  • Zhang JW, Lazarow PB. PEB1 (PAS7) in Saccharomyces cerevisiae encodes a hydrophilic, intra-peroxisomal protein that is a member of the WD repeat family and is essential for the import of thiolase into peroxisomes. J Cell Biol. 1995 Apr;129(1):65–80. [PMC free article] [PubMed]

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