Home LiteratureArticle Details
PMID: 10359594 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Pex19p interacts with Pex3p and Pex10p and is essential for peroxisome biogenesis in Pichia pastoris.

Molecular biology of the cell ·Vol. 10 ·No. 6 ·1999-06-00 ·Pages 1745-61

Snyder WB, Faber KN, Wenzel TJ, Koller A, Lüers GH, Rangell L, Keller GA, Subramani S

Abstract

We report the cloning and characterization of Pichia pastoris PEX19 by complementation of a peroxisome-deficient mutant strain. Import of peroxisomal targeting signal 1- and 2-containing peroxisomal matrix proteins is defective in pex19 mutants. PEX19 encodes a hydrophilic 299-amino acid protein with sequence similarity to Saccharomyces cerevisiae Pex19p and human and Chinese hamster PxF, all farnesylated proteins, as well as hypothetical proteins from Caenorhabditis elegans and Schizosaccharomyces pombe. The farnesylation consensus is conserved in PpPex19p but dispensable for function and appears unmodified under the conditions tested. Pex19p localizes predominantly to the cytosolic fraction. Biochemical and two-hybrid analyses confirmed that Pex19p interacts with Pex3p, as seen in S. cerevisiae, but unexpectedly also with Pex10p. Two-hybrid analysis demonstrated that the amino-terminal 42 amino acids of Pex19p interact with the carboxyl-terminal 335 amino acids of Pex3p. In addition, the extreme carboxyl terminus of Pex19p (67 amino acids) is required for interaction with the amino-terminal 380 amino acids of Pex10p. Biochemical and immunofluorescence microscopy analyses of pex19Delta cells identified the membrane protein Pex3p in peroxisome remnants that were not previously observed in S. cerevisiae. These small vesicular and tubular (early) remnants are morphologically distinct from other Pppex mutant (late) remnants, suggesting that Pex19p functions at an early stage of peroxisome biogenesis.

MeSH Terms
ATP-Binding Cassette Transporters Amino Acid Sequence Animals Binding Sites Cricetinae Cricetulus Cytosol/metabolism Fungal Proteins/genetics,metabolism Humans Membrane Proteins/genetics,metabolism Microbodies/metabolism Molecular Sequence Data Mutation Peroxins Pichia/genetics,metabolism Receptors, Cytoplasmic and Nuclear/genetics,metabolism Saccharomyces cerevisiae Proteins Selection, Genetic Sequence Homology, Amino Acid Ubiquitin-Protein Ligases
Chemicals
ATP-Binding Cassette Transporters Fungal Proteins Membrane Proteins PEX10 protein, S cerevisiae PEX10 protein, human PEX3 protein, S cerevisiae Peroxins Receptors, Cytoplasmic and Nuclear SPF1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Ubiquitin-Protein Ligases
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Snyder W B
Department of Biology, University of California, San Diego, La Jolla, California 92093-0322, USA.
Faber K N
Wenzel T J
Koller A
Lüers G H
Rangell L
Keller G A
Subramani S
References (55)
55 references, click to expand
  1. A unified nomenclature for peroxisome biogenesis factors.
    J Cell Biol. 1996 Oct;135(1):1-3 PMID: 8858157
  2. Microbodies: peroxisomes and glyoxysomes.
    J Cell Biol. 1981 Dec;91(3 Pt 2):271s-283s PMID: 7033240
  3. The peroxisome in retrospect.
    Ann N Y Acad Sci. 1996 Dec 27;804:1-10 PMID: 8993531
  4. Protein import into peroxisomes: new developments.
    Ann N Y Acad Sci. 1996 Dec 27;804:34-46 PMID: 8993534
  5. PEX genes on the rise.
    Nat Genet. 1997 Apr;15(4):331-3 PMID: 9090374
  6. Endosomal transport function in yeast requires a novel AAA-type ATPase, Vps4p.
    EMBO J. 1997 Apr 15;16(8):1820-31 PMID: 9155008
  7. Genomic organization and molecular characterization of a gene encoding HsPXF, a human peroxisomal farnesylated protein.
    Genomics. 1997 Oct 1;45(1):200-10 PMID: 9339377
  8. 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
  9. Labeling of peroxisomes with green fluorescent protein in living P. pastoris cells.
    J Histochem Cytochem. 1996 Jun;44(6):581-9 PMID: 8666743
  10. Characterization of a novel component of the peroxisomal protein import apparatus using fluorescent peroxisomal proteins.
    EMBO J. 1996 Jul 1;15(13):3275-85 PMID: 8670828
  11. 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
  12. Analysis of the carboxyl-terminal peroxisomal targeting signal 1 in a homologous context in Saccharomyces cerevisiae.
    J Biol Chem. 1996 Oct 18;271(42):26375-82 PMID: 8824293
  13. Pex19p, a farnesylated protein essential for peroxisome biogenesis.
    Mol Cell Biol. 1998 Jan;18(1):616-28 PMID: 9418908
  14. 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
  15. Two AAA family peroxins, PpPex1p and PpPex6p, interact with each other in an ATP-dependent manner and are associated with different subcellular membranous structures distinct from peroxisomes.
    Mol Cell Biol. 1998 Feb;18(2):936-43 PMID: 9447990
  16. Components involved in peroxisome import, biogenesis, proliferation, turnover, and movement.
    Physiol Rev. 1998 Jan;78(1):171-88 PMID: 9457172
  17. A mobile PTS2 receptor for peroxisomal protein import in Pichia pastoris.
    J Cell Biol. 1998 Feb 23;140(4):807-20 PMID: 9472033
  18. Peroxisome degradation by microautophagy in Pichia pastoris: identification of specific steps and morphological intermediates.
    J Cell Biol. 1998 May 4;141(3):625-36 PMID: 9566964
  19. The Vps4p AAA ATPase regulates membrane association of a Vps protein complex required for normal endosome function.
    EMBO J. 1998 Jun 1;17(11):2982-93 PMID: 9606181
  20. 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
  21. A versatile set of vectors for constitutive and regulated gene expression in Pichia pastoris.
    Yeast. 1998 Jun 15;14(8):783-90 PMID: 9675822
  22. Pex20p of the yeast Yarrowia lipolytica is required for the oligomerization of thiolase in the cytosol and for its targeting to the peroxisome.
    J Cell Biol. 1998 Jul 27;142(2):403-20 PMID: 9679140
  23. Identification of PEX10, the gene defective in complementation group 7 of the peroxisome-biogenesis disorders.
    Am J Hum Genet. 1998 Aug;63(2):347-59 PMID: 9683594
  24. The endoplasmic reticulum plays an essential role in peroxisome biogenesis.
    Trends Biochem Sci. 1998 Jul;23(7):231-3 PMID: 9697407
  25. Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body.
    Cell. 1998 Dec 11;95(6):847-58 PMID: 9865702
  26. Glycerolipid biosynthesis in peroxisomes via the acyl dihydroxyacetone phosphate pathway.
    Ann N Y Acad Sci. 1982;386:170-82 PMID: 7046569
  27. Isolation of alcohol oxidase and two other methanol regulatable genes from the yeast Pichia pastoris.
    Mol Cell Biol. 1985 May;5(5):1111-21 PMID: 3889590
  28. Biogenesis of peroxisomes.
    Annu Rev Cell Biol. 1985;1:489-530 PMID: 3916321
  29. Identification of a peroxisomal targeting signal at the carboxy terminus of firefly luciferase.
    J Cell Biol. 1987 Dec;105(6 Pt 2):2923-31 PMID: 3480287
  30. A conserved tripeptide sorts proteins to peroxisomes.
    J Cell Biol. 1989 May;108(5):1657-64 PMID: 2654139
  31. Rat liver peroxisomes catalyze the initial step in cholesterol synthesis. The condensation of acetyl-CoA units into acetoacetyl-CoA.
    J Biol Chem. 1990 Apr 5;265(10):5731-5 PMID: 1969406
  32. 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
  33. A novel, cleavable peroxisomal targeting signal at the amino-terminus of the rat 3-ketoacyl-CoA thiolase.
    EMBO J. 1991 Nov;10(11):3255-62 PMID: 1680677
  34. 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):947-54 PMID: 1764107
  35. Development of the yeast Pichia pastoris as a model organism for a genetic and molecular analysis of peroxisome assembly.
    Yeast. 1992 Aug;8(8):613-28 PMID: 1441741
  36. A membrane-associated complex containing the Vps15 protein kinase and the Vps34 PI 3-kinase is essential for protein sorting to the yeast lysosome-like vacuole.
    EMBO J. 1993 May;12(5):2195-204 PMID: 8387919
  37. The pas8 mutant of Pichia 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. 1993 May;121(4):761-74 PMID: 8098333
  38. Cloning and characterization of PAS5: a gene required for peroxisome biogenesis in the methylotrophic yeast Pichia pastoris.
    J Cell Biol. 1993 Nov;123(3):535-48 PMID: 8227124
  39. An efficient positive selection procedure for the isolation of peroxisomal import and peroxisome assembly mutants of Saccharomyces cerevisiae.
    Genetics. 1993 Nov;135(3):731-40 PMID: 7507454
  40. PxF, a prenylated protein of peroxisomes.
    J Biol Chem. 1994 May 13;269(19):14182-90 PMID: 8188701
  41. Sequence of a putative human housekeeping gene (HK33) localized on chromosome 1.
    Gene. 1994 Sep 2;146(2):291-5 PMID: 8076834
  42. Role of the PAS1 gene of Pichia pastoris in peroxisome biogenesis.
    J Cell Biol. 1994 Dec;127(5):1259-73 PMID: 7962088
  43. The Hansenula polymorpha PER8 gene encodes a novel peroxisomal integral membrane protein involved in proliferation.
    J Cell Biol. 1995 Feb;128(3):307-19 PMID: 7844145
  44. PER3, a gene required for peroxisome biogenesis in Pichia pastoris, encodes a peroxisomal membrane protein involved in protein import.
    J Biol Chem. 1995 May 5;270(18):10940-51 PMID: 7738036
  45. Formation of the peroxisome lumen is abolished by loss of Pichia pastoris Pas7p, a zinc-binding integral membrane protein of the peroxisome.
    Mol Cell Biol. 1995 Nov;15(11):6406-19 PMID: 7565793
  46. Identification of peroxisomal membrane ghosts with an epitope-tagged integral membrane protein in yeast mutants lacking peroxisomes.
    Yeast. 1995 Sep 15;11(11):1045-60 PMID: 7502580
  47. The Pichia 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. 1996 May;16(5):2527-36 PMID: 8628321
  48. 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
  49. Pex18p and Pex21p, a novel pair of related peroxins essential for peroxisomal targeting by the PTS2 pathway.
    J Cell Biol. 1998 Dec 28;143(7):1859-69 PMID: 9864360
  50. A vital stain for studying membrane dynamics in bacteria: a novel mechanism controlling septation during Bacillus subtilis sporulation.
    Mol Microbiol. 1999 Feb;31(4):1149-59 PMID: 10096082
  51. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  52. A fatty acyl-CoA oxidizing system in rat liver peroxisomes; enhancement by clofibrate, a hypolipidemic drug.
    Proc Natl Acad Sci U S A. 1976 Jun;73(6):2043-6 PMID: 180535
  53. DNA sequencing with chain-terminating inhibitors.
    Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463-7 PMID: 271968
  54. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  55. 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
Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.10.6.1745
Published
1999-06-00
Pages
1745-61
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC25367
Subset
IM
Grants
NIDDK NIH HHS · DK-41737 · United States
Databases
GENBANK
AF133271
External Links
PubMed source DOI: 10.1091/mbc.10.6.1745 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2