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The cytosolic and membrane components required for peroxisomal protein import

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Abstract

Peroxisomes are vital intracellular organelles which house enzymes involved in a variety of metabolic pathways. The large number of human disorders associated with flawed peroxisome biogenesis emphasizes the importance of protein targeting to, and translocation across, the peroxisomal membrane. This brief review will summarize some of the emerging themes of peroxisomal protein import, specifically addressing the targeting signals possessed by constituent proteins, as well as the cytosolic, membrane and luminal components of the import machinery. Although a detailed understanding of the molecular mechanisms of peroxisomal protein import is not yet available, remarkable progress has been made in the field in recent years. An overview of these advances will be presented.

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References

  1. Subramani S. (1993) Protein import into peroxisomes and biogenesis of the organelle. Annu. Rev. Cell Biol.9: 445–478

    Article  PubMed  Google Scholar 

  2. McCollum D., Monosov E. and Subramani S. (1993) Thepas8 mutant ofPichia pastoris exhibits the peroxisomal protein import deficiencies of Zellweger syndrome cells: the PAS8 protein binds to the COOH-terminal tripeptide peroxisomal targeting signal, and is a member of the TPR protein family. J. Cell. Biol.121: 761–774

    Article  PubMed  Google Scholar 

  3. Terlecky S. R., Nuttley W. M., McCollum D., Sock E. and Subramani S. (1995) ThePichia pastoris peroxisomal protein PAS8p is the receptor for the C-terminal tripeptide peroxisomal targeting signal. EMBO J.14: 3627–3634

    PubMed  Google Scholar 

  4. Swinkels, B. W., Gould, S. J., Bodnar, A. G., Rachubinski R. A. and Subramani S. (1991) A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase. EMBO J.10: 3255–3262

    PubMed  Google Scholar 

  5. Osumi, T., Tsukamoto T., Hata S., Miura S., Fujiki Y. et al. (1991) Amino-terminal presequence of the precursor of peroxisomal 3-ketoacyl-CoA thiolase is a cleavable signal peptide for peroxisomal targeting. Biochem. Biophys. Res. Commun.181: 947–954

    Article  PubMed  Google Scholar 

  6. Glover J. R., Andrews D. W., Subramani S. and Rachubinski R. A. (1994) Mutagenesis of the amino targeting signal ofSaccharomyces cerevisiae 3-ketoacyl-CoA thiolase reveals conserved amino acids required for import into peroxisomes in vivo. J. Biol. Chem.269: 7558–7563

    PubMed  Google Scholar 

  7. Erdmann R. (1994) The peroxisomal targeting signal of 3-oxoacyl-CoA thiolase fromSaccharomyces cerevisiae. Yeast10: 935–944

    Article  PubMed  Google Scholar 

  8. Rehling P., Skaletz-Rorowski A., Franse M., Veenhuis M and Kunau W.-H. (1995) Pas6p or how to get into the peroxisome. Eur. J. Cell Biol. ECBO Meeting Heidelberg (Abstract)

  9. Distel B., Erdmann R., Gould S. J., Blobel G., Crane D. I., Cregg J. M. et al. (1996) A unified nomenclature for peroxisome biogenesis. J. Cell Biol.135: 1–3

    Article  PubMed  Google Scholar 

  10. Waterham H. R., Titorenko V. I., Haima P., Cregg J. M., Harder W. and Veenhuis M. (1994) TheHansenula polymorpha PER1 gene is essential for peroxisome biogenesis and encodes a peroxisomal matrix protein with both carboxy- and amino-terminal 14 targeting signals. J. Cell Biol.127: 737–749

    Article  PubMed  Google Scholar 

  11. Faber K. N., Keizer G. I., Pluim D., Harder W., Ab G. and Veenhuis M. (1995) The N-terminus of amine oxidase ofHansenula polymorpha contains a peroxisomal targeting signal. FEBS Lett.357: 115–120

    Article  PubMed  Google Scholar 

  12. Gietl C., Faber K. N., van der Klei I. J. and Veenhuis M. (1994) Mutational analysis of the N-terminal topogenic signal of watermelon glyoxysomal malate dehydrogenase using the heterologous hostHansenula polymorpha. Proc. Natl. Acad. Sci. USA91: 3151–3155

    PubMed  Google Scholar 

  13. Blattner J., Dorsam H. and Clatyon C. E. (1995) Function of N-terminal import signals in trypanosome microbodies. FEBS Lett.360: 310–314

    Article  PubMed  Google Scholar 

  14. Marzioch M., Erdmann R., Veenhuis M. and Kunau W. H. (1994)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.13: 4908–4918

    PubMed  Google Scholar 

  15. Zhang, J. W. and Lazarow P. B. (1995) PEB1 (PAS7) inSaccharomyces 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.129: 65–80

    Article  PubMed  Google Scholar 

  16. Zhang J. W. and Lazarow P. B. (1996) Peblp (Pas7p) is an 15 intraperoxisomal receptor for the NH2-terminal, type 2, peroxisomal targeting signal of thiolase: Peb1p itself is targeted to peroxisomes by an NH2-terminal peptide. J. Cell Biol.132: 325–334

    Article  PubMed  Google Scholar 

  17. Rehling P. Marzioch M., Niesen F., Wittke E., Veenhuis M. and Kunau W. (1996) The import receptor for the peroxisomal targeting signal 2 (PTS2) inSaccharomyces cerevisiae is encoded by the PAS7 gene. EMBO J.15: 2901–2913

    PubMed  Google Scholar 

  18. Small G. M., Szabo L. J. and Lazarow P. B. (1988) Acyl-CoA oxidase contains two targeting sequences each of which can mediate protein import into peroxisomes. EMBO J.7: 1167–1173

    PubMed  Google Scholar 

  19. Kragler F., Langeder A., Raupachova J. Binder M. and Hartig A. (1993) Two independent peroxisomal targeting signals in catalase A ofSaccharomyces cerevisiae. J. Cell Biol.120: 665–673

    Article  PubMed  Google Scholar 

  20. Elgersma Y., van Roermund C.W., Wanders R. J. and Tabak H. F. (1995) Peroxisomal and mitochondrial carnitine acetyltransferases ofSaccharomyces cerevisiae are encoded by a single gene. EMBO J.14: 3472–3479

    PubMed  Google Scholar 

  21. Glover J. R., AndrewsD. W. and Rachubinski R. A. (1994) 16Saccharomyces cerevisiae peroxisomal thiolase is imported as a dimer. Proc. Natl. Acad. Sci. USA91: 10541–10545

    PubMed  Google Scholar 

  22. McNew J. A. and Goodman J. M. (1994) An oligomeric protein is imported into peroxisomes in vivo. J. Cell Biol.127: 1245–1257

    Article  PubMed  Google Scholar 

  23. Wiemer E. A. C., Luers G., Faber K. N., Wenzel T., Veenhuis M. and Subramani S. (1996) Isolation and characterization of Pas2p, a peroxisomal membrane protein essential for peroxisome biogenesis in the methylotrophic yeastPichia pastoris. J. Biol. Chem.271: 18973–18980

    Article  PubMed  Google Scholar 

  24. McNew J. A. and Goodman J. M. (1996), The targeting and assembly of peroxisomal proteins: some old rules do not apply. TIBS21: 54–58

    PubMed  Google Scholar 

  25. Brocard C., Kragler F., Simon M. M., Schuster T. and Hartig A. (1994) The tetratricopeptide repeat-domain of the PAS10 protein ofSaccharomyces cerevisiae is essential for binding the peroxisomal targeting signal-SKL. Biochem. Biophys. Res. Commun.204: 1016–1022

    Article  PubMed  Google Scholar 

  26. Van der Leij I., Franse M. M., Elgersma Y., Distel B. and Tabak H. F. (1993) PAS10 is a tetratricopeptide-repeat protein that is essential for the import of most matrix proteins into peroxisomes ofSaccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA90: 11782–11786

    PubMed  Google Scholar 

  27. Van der Klei I. J., Hilbrands R. E., Swaving G. J., Waterham H. R., Vrieling E. G., Titorenko V. I. et al. (1995) TheHansenula polymorpha PER3 gene is essential for the import of PTS1 proteins into the peroxisomal matrix. J. Biol. Chem.270: 17229–17236

    Article  PubMed  Google Scholar 

  28. Nuttley W. M., Szilard R. K., Smith J. J., Veenhuis M. and Rachubinski R. A. (1995) ThePAH2 gene is required for peroxisome assembly in the methylotrophic yeastHansenula polymorpha and encodes a member of the tetratricopeptide repeat family of proteins. Gene160: 33–39

    Article  PubMed  Google Scholar 

  29. Szilard R. K., Titorenko V. I., Veenhuis M. and Rachubinski R. A. (1995) Pay32p of the yeastYarrowia lipolytica is an intraperoxisomal component of the matrix protein translocation machinery. J. Cell Biol.131: 1453–1469

    Article  PubMed  Google Scholar 

  30. Dodt G., Braverman N., Wong C., Moser A., Moser H. W., Watkins P. et al. (1995) Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders. Nature Genet.9: 115–125

    Article  PubMed  Google Scholar 

  31. Wiemer E. A., Nuttley W. M. Bertolaet B. L., Li X., Francke U., Wheelock M. J. et al. (1995) Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. J. Cell Biol.130: 51–65

    Article  PubMed  Google Scholar 

  32. Fransen M., Brees C., Baumgart E., Vanhooren J. C., Baes M., Mannaerts G. P. et al. (1995) Identification and characterization of the putative human peroxisomal C-terminal targeting signal import receptor. J. Biol. Chem.270: 7731–7736.

    PubMed  Google Scholar 

  33. Rachubinski R. A. and Subramani S. (1995) How proteins penetrate peroxisomes. Cell83: 525–528

    Article  PubMed  Google Scholar 

  34. Elgersma Y., Kwast L., Klein A., Voorn-Brouwer T., Van den Berg M., Metzig B., America T. et al. (1996) The SH3 domain of theSaccharomyces cerevisiae peroxisomal membrane protein Pex13p functions as a docking site for Pex5p, a mobile receptor for the import of PTS1 containing proteins. J. Cell Biol.135: 97–109

    Article  PubMed  Google Scholar 

  35. Erdmann R. and Blobel G. (1996) Identification of Pex13p, a peroxisomal membrane receptor for the PTS1 recognition factor. J. Cell Biol.135: 111–121

    Article  PubMed  Google Scholar 

  36. Gould S. J., Kalish J. E., Morell J. C., Bjorkman J., Urquhart A. J. and Crane D. I. (1996) An SH3 protein in the peroxisomal membrane is a docking factor for the PTS1 receptor. J. Cell Biol.135: 85–95

    Article  PubMed  Google Scholar 

  37. Tsukamoto T., Miura S. and Fujiki Y. (1991) Restoration by a 35K membrane protein of peroxisome assembly in a peroxisome-deficient mammalian cell mutant. Nature350: 77–81

    Article  PubMed  Google Scholar 

  38. Kalish J. E., Theda C., Morrell J. C., Berg J. M. and Gould S. J. (1995), Formation of the peroxisome lumen is abolished by loss ofPichia pastoris Pas7p, a zinc-binding integral membrane protein of the peroxisome. Mol. Cell Biol.15: 6406–6419

    PubMed  Google Scholar 

  39. Waterham H. R., de Vries Y., Russel K. A., Xie W., Veenhuis M. and Cregg J. M. (1996) ThePichia pastoris PER6 gene product is a peroxisomal integral membrane protein essential for peroxisome biogenesis and has sequence similarity to the Zellweger syndrome protein PAF-1. Mol. Cell Biol.16: 2527–2536

    PubMed  Google Scholar 

  40. Kalish J. E., Keller G.-A., Morell J. C., Mihalik S. J., Smith B., Cregg J. M. et al. (1996) Characterization of a novel component of the peroxisomal protein import apparatus using fluorescent peroxisomal proteins. EMBO J.15: 3275–3285

    PubMed  Google Scholar 

  41. Walton P. A., Hill P. E. and Subramani S. (1995) Import of stably folded proteins into peroxisomes. Mol. Biol. Cell6: 675–683

    PubMed  Google Scholar 

  42. Walton P. A., Wendland M., Subramani S., Rachubinski R. A. and Welch W. J. (1994) Involvement of 70-kD heat-shock 20 proteins in peroxisomal import. J. Cell Biol.125: 1037–1046

    PubMed  Google Scholar 

  43. Imanaka T., Small G. M. and Lazarow P. B. (1987) Translocation of acyl-CoA oxidase into peroxisomes requires ATP hydrolysis but not a membrane potential. J. Cell Biol.105: 2915–2922

    Article  PubMed  Google Scholar 

  44. Wendland M. and Subramani S. (1993) Cytosol-dependent peroxisomal protein import in a permeabilized cell system. J. Cell Biol.120: 675–685

    Article  PubMed  Google Scholar 

  45. Diestelkotter P. and Just W. W. (1993) In vitro insertion of the 22-kD peroxisomal membrane protein into isolated rat liver peroxisomes. J. Cell Biol.123: 1717–1725

    Article  PubMed  Google Scholar 

  46. Imanaka T., Shiina Y., Takano T., Hashimoto T. and Osumi T. (1996) Insertion of the 70-kDa peroxisomal membrane protein into peroxisomal membranes in vivo and in vitro. J. Biol. Chem.271: 3706–3713

    Article  PubMed  Google Scholar 

  47. Novikoff A. B. and Shin W. (1964) The endoplasmic reticulum in the Golgi zone and its relations to microbodies, Golgi apparatus and autophagic vacuoles in rat liver cells. J. Microscopie3: 187–206

    Google Scholar 

  48. Lazarow P. B. and Fujiki Y. (1985) Biogenesis of peroxisomes. Annu. Rev. Cell Biol.1: 489–530

    Article  PubMed  Google Scholar 

  49. Bodnar A. G. and Rachubinski R. A. (1991) Characterization of the integral membrane polypeptides of rat liver peroxisomes isolated from untreated and clofibrate-treated rats. Biochem. Cell Biol.69: 499–508

    PubMed  Google Scholar 

  50. Elgersma Y. (1995) Transport of proteins and metabolites across the peroxisomal membrane inSaccharomyxes cerevisiae. Ph.D. Thesis, University of Amsterdam

  51. Baerends R. J. S., Rasmussen S. W., Hilbrands R. E., van der Heide M., Faber K. N., Reuvekamp P. T. W. et al. (1996) TheHansenula polymorpha PER9 gene encodes a peroxisomal membrane protein essential for peroxisome assembly and integrity. J. Biol. Chem.271: 8887–8894

    Article  PubMed  Google Scholar 

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  1. Department of Biology, University of California, San Diego, 9500 Gilman Drive, 92093-0322, La Jolla, California, USA

    S. R. Terlecky, W. M. Nuttley & S. Subramani

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  1. S. R. Terlecky
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  3. S. Subramani
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Terlecky, S.R., Nuttley, W.M. & Subramani, S. The cytosolic and membrane components required for peroxisomal protein import. Experientia 52, 1050–1054 (1996). https://doi.org/10.1007/BF01952101

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