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PMID: 10637226 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Saccharomyces cerevisiae pex3p and pex19p are required for proper localization and stability of peroxisomal membrane proteins.

The EMBO journal ·Vol. 19 ·No. 2 ·2000-01-17 ·Pages 223-33

Hettema EH, Girzalsky W, van Den Berg M, Erdmann R, Distel B

Abstract

The mechanisms by which peroxisomal membrane proteins (PMPs) are targeted to and inserted into membranes are unknown, as are the required components. We show that among a collection of 16 Saccharomyces cerevisiae peroxisome biogenesis (pex) mutants, two mutants, pex3Delta and pex19Delta, completely lack detectable peroxisomal membrane structures and mislocalize their PMPs to the cytosol where they are rapidly degraded. The other pexDelta mutants contain membrane structures that are properly inherited during vegetative growth and that house multiple PMPs. Even Pex15p requires Pex3p and Pex19p for localization to peroxisomal membranes. This PMP was previously hypothesized to travel via the endoplasmic reticulum (ER) to peroxisomes. We provide evidence that ER-accumulated Pex15p is not a sorting intermediate on its way to peroxisomes. Our results show that Pex3p and Pex19p are required for the proper localization of all PMPs tested, including Pex15p, whereas the other Pex proteins might only be required for targeting/import of matrix proteins.

MeSH Terms
ATP-Binding Cassette Transporters Cytosol/metabolism Endoplasmic Reticulum/metabolism Fungal Proteins/genetics,metabolism Gene Deletion Kinetics Membrane Proteins/genetics,metabolism Microscopy, Electron Mutagenesis Peroxins Peroxisomes/physiology,ultrastructure Saccharomyces cerevisiae/genetics,physiology,ultrastructure Saccharomyces cerevisiae Proteins
Chemicals
ATP-Binding Cassette Transporters Fungal Proteins Membrane Proteins PEX19 protein, S cerevisiae PEX3 protein, S cerevisiae Peroxins SPF1 protein, S cerevisiae Saccharomyces cerevisiae Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hettema E H
Department of Biochemistry, University of Amsterdam, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Girzalsky W
van Den Berg M
Erdmann R
Distel B
References (60)
60 references, click to expand
  1. Components of the yeast spindle and spindle pole body.
    J Cell Biol. 1990 Nov;111(5 Pt 1):1913-27 PMID: 2229181
  2. The sorting sequence of the peroxisomal integral membrane protein PMP47 is contained within a short hydrophilic loop.
    J Cell Biol. 1996 Apr;133(2):269-80 PMID: 8609161
  3. Import of proteins into peroxisomes.
    Biochim Biophys Acta. 1999 Aug 12;1451(1):17-34 PMID: 10446385
  4. The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor.
    EMBO J. 1996 Jun 17;15(12):2914-23 PMID: 8670792
  5. Pex19p interacts with Pex3p and Pex10p and is essential for peroxisome biogenesis in Pichia pastoris.
    Mol Biol Cell. 1999 Jun;10(6):1745-61 PMID: 10359594
  6. Pmp27 promotes peroxisomal proliferation.
    J Cell Biol. 1995 Apr;129(2):345-55 PMID: 7721939
  7. Pex13p is an SH3 protein of the peroxisome membrane and a docking factor for the predominantly cytoplasmic PTs1 receptor.
    J Cell Biol. 1996 Oct;135(1):85-95 PMID: 8858165
  8. The ABC transporter proteins Pat1 and Pat2 are required for import of long-chain fatty acids into peroxisomes of Saccharomyces cerevisiae.
    EMBO J. 1996 Aug 1;15(15):3813-22 PMID: 8670886
  9. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae.
    Yeast. 1994 Dec;10(13):1793-808 PMID: 7747518
  10. Biogenesis of peroxisomes.
    Annu Rev Cell Biol. 1985;1:489-530 PMID: 3916321
  11. Characterization of the integral membrane polypeptides of rat liver peroxisomes isolated from untreated and clofibrate-treated rats.
    Biochem Cell Biol. 1991 Aug;69(8):499-508 PMID: 1760154
  12. Saccharomyces cerevisiae peroxisomal thiolase is imported as a dimer.
    Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10541-5 PMID: 7937990
  13. An oligomeric protein is imported into peroxisomes in vivo.
    J Cell Biol. 1994 Dec;127(5):1245-57 PMID: 7962087
  14. The cytosolic DnaJ-like protein djp1p is involved specifically in peroxisomal protein import.
    J Cell Biol. 1998 Jul 27;142(2):421-34 PMID: 9679141
  15. 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):311-24 PMID: 8636210
  16. Transport route for synaptobrevin via a novel pathway of insertion into the endoplasmic reticulum membrane.
    EMBO J. 1995 Jan 16;14(2):217-23 PMID: 7835332
  17. Peroxisomes: simple in function but complex in maintenance.
    Trends Cell Biol. 1999 Nov;9(11):447-53 PMID: 10511709
  18. Insertion of the 70-kDa peroxisomal membrane protein into peroxisomal membranes in vivo and in vitro.
    J Biol Chem. 1996 Feb 16;271(7):3706-13 PMID: 8631984
  19. Peroxisomal membrane ghosts in Zellweger syndrome--aberrant organelle assembly.
    Science. 1988 Mar 25;239(4847):1536-8 PMID: 3281254
  20. Pex14p, a peroxisomal membrane protein binding both receptors of the two PTS-dependent import pathways.
    Cell. 1997 Apr 4;89(1):83-92 PMID: 9094717
  21. Import of stably folded proteins into peroxisomes.
    Mol Biol Cell. 1995 Jun;6(6):675-83 PMID: 7579687
  22. The import receptor for the peroxisomal targeting signal 2 (PTS2) in Saccharomyces cerevisiae is encoded by the PAS7 gene.
    EMBO J. 1996 Jun 17;15(12):2901-13 PMID: 8670791
  23. Cytosolic factors mediate protein insertion into the peroxisomal membrane.
    FEBS Lett. 1997 Sep 1;414(1):95-8 PMID: 9305739
  24. A mobile PTS2 receptor for peroxisomal protein import in Pichia pastoris.
    J Cell Biol. 1998 Feb 23;140(4):807-20 PMID: 9472033
  25. The SH3 domain of the Saccharomyces cerevisiae peroxisomal membrane protein Pex13p functions as a docking site for Pex5p, a mobile receptor for the import PTS1-containing proteins.
    J Cell Biol. 1996 Oct;135(1):97-109 PMID: 8858166
  26. Synthesis of a major integral membrane polypeptide of rat liver peroxisomes on free polysomes.
    Proc Natl Acad Sci U S A. 1984 Nov;81(22):7127-31 PMID: 6594687
  27. Pex17p of Saccharomyces cerevisiae is a novel peroxin and component of the peroxisomal protein translocation machinery.
    J Cell Biol. 1998 Jan 12;140(1):49-60 PMID: 9425153
  28. Newly identified Chinese hamster ovary cell mutants are defective in biogenesis of peroxisomal membrane vesicles (Peroxisomal ghosts), representing a novel complementation group in mammals.
    J Biol Chem. 1998 Sep 11;273(37):24122-30 PMID: 9727033
  29. Components involved in peroxisome import, biogenesis, proliferation, turnover, and movement.
    Physiol Rev. 1998 Jan;78(1):171-88 PMID: 9457172
  30. Recombinant human peroxisomal targeting signal receptor PEX5. Structural basis for interaction of PEX5 with PEX14.
    J Biol Chem. 1999 Feb 26;274(9):5666-73 PMID: 10026185
  31. 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):4908-18 PMID: 7957058
  32. Peroxisomes: Organelles at the crossroads.
    Trends Cell Biol. 1997 Oct;7(10):400-7 PMID: 17708989
  33. The Hansenula polymorpha PER9 gene encodes a peroxisomal membrane protein essential for peroxisome assembly and integrity.
    J Biol Chem. 1996 Apr 12;271(15):8887-94 PMID: 8621531
  34. Differential protein import deficiencies in human peroxisome assembly disorders.
    J Cell Biol. 1994 May;125(4):755-67 PMID: 7910611
  35. Purification and immunolocalization of the peroxisomal 3-oxoacyl-CoA thiolase from Saccharomyces cerevisiae.
    Yeast. 1994 Sep;10(9):1173-82 PMID: 7754706
  36. Isolation and biochemical characterization of organelles from the yeast, Saccharomyces cerevisiae.
    Yeast. 1995 May;11(6):493-536 PMID: 7645343
  37. The carboxyl-terminal tripeptide serine-lysine-leucine of firefly luciferase is necessary but not sufficient for peroxisomal import in yeast.
    New Biol. 1992 Feb;4(2):157-65 PMID: 1554690
  38. A unified nomenclature for peroxisome biogenesis factors.
    J Cell Biol. 1996 Oct;135(1):1-3 PMID: 8858157
  39. Overexpression of Pex15p, a phosphorylated peroxisomal integral membrane protein required for peroxisome assembly in S.cerevisiae, causes proliferation of the endoplasmic reticulum membrane.
    EMBO J. 1997 Dec 15;16(24):7326-41 PMID: 9405362
  40. Biosynthesis of membrane polypeptides of rat liver peroxisomes.
    J Biochem. 1987 Feb;101(2):491-6 PMID: 3584097
  41. Identification of a human PTS1 receptor docking protein directly required for peroxisomal protein import.
    Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8087-92 PMID: 9653144
  42. Cloning and characterization of the gene encoding the human peroxisomal assembly protein Pex3p.
    FEBS Lett. 1998 Jun 5;429(1):53-60 PMID: 9657383
  43. Pex14p is a member of the protein linkage map of Pex5p.
    EMBO J. 1997 Sep 15;16(18):5491-500 PMID: 9312008
  44. The ubiquitin-conjugating enzyme Pex4p of Hansenula polymorpha is required for efficient functioning of the PTS1 import machinery.
    EMBO J. 1998 Jul 1;17(13):3608-18 PMID: 9649431
  45. Mutation in PEX16 is causal in the peroxisome-deficient Zellweger syndrome of complementation group D.
    Am J Hum Genet. 1998 Dec;63(6):1622-30 PMID: 9837814
  46. Giant peroxisomes in oleic acid-induced Saccharomyces cerevisiae lacking the peroxisomal membrane protein Pmp27p.
    J Cell Biol. 1995 Feb;128(4):509-23 PMID: 7860627
  47. Peroxisome synthesis in the absence of preexisting peroxisomes.
    J Cell Biol. 1999 Jan 25;144(2):255-66 PMID: 9922452
  48. Enlarged peroxisomes are present in oleic acid-grown Yarrowia lipolytica overexpressing the PEX16 gene encoding an intraperoxisomal peripheral membrane peroxin.
    J Cell Biol. 1997 Jun 16;137(6):1265-78 PMID: 9182661
  49. The Pex16p homolog SSE1 and storage organelle formation in Arabidopsis seeds.
    Science. 1999 Apr 9;284(5412):328-30 PMID: 10195899
  50. Identification of Pex13p a peroxisomal membrane receptor for the PTS1 recognition factor.
    J Cell Biol. 1996 Oct;135(1):111-21 PMID: 8858167
  51. The syntaxin Tlg1p mediates trafficking of chitin synthase III to polarized growth sites in yeast.
    Mol Biol Cell. 1998 Dec;9(12):3383-97 PMID: 9843576
  52. 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;72:248-54 PMID: 942051
  53. In vitro insertion of the 22-kD peroxisomal membrane protein into isolated rat liver peroxisomes.
    J Cell Biol. 1993 Dec;123(6 Pt 2):1717-25 PMID: 8276892
  54. Pex19p, a farnesylated protein essential for peroxisome biogenesis.
    Mol Cell Biol. 1998 Jan;18(1):616-28 PMID: 9418908
  55. The endoplasmic reticulum plays an essential role in peroxisome biogenesis.
    Trends Biochem Sci. 1998 Jul;23(7):231-3 PMID: 9697407
  56. PAS3, a Saccharomyces cerevisiae gene encoding a peroxisomal integral membrane protein essential for peroxisome biogenesis.
    J Cell Biol. 1991 Sep;114(6):1167-78 PMID: 1894692
  57. Involvement of Pex13p in Pex14p localization and peroxisomal targeting signal 2-dependent protein import into peroxisomes.
    J Cell Biol. 1999 Mar 22;144(6):1151-62 PMID: 10087260
  58. Multiple PEX genes are required for proper subcellular distribution and stability of Pex5p, the PTS1 receptor: evidence that PTS1 protein import is mediated by a cycling receptor.
    J Cell Biol. 1996 Dec;135(6 Pt 2):1763-74 PMID: 8991089
  59. Isolation and characterization of Pas2p, a peroxisomal membrane protein essential for peroxisome biogenesis in the methylotrophic yeast Pichia pastoris.
    J Biol Chem. 1996 Aug 2;271(31):18973-80 PMID: 8702562
  60. Human PEX19: cDNA cloning by functional complementation, mutation analysis in a patient with Zellweger syndrome, and potential role in peroxisomal membrane assembly.
    Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2116-21 PMID: 10051604
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.2.223
Published
2000-01-17
Pages
223-33
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305556
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.2.223 PMC Full Text View journal details
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