This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Collins, C. S.
Right arrow Articles by Gould, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Collins, C. S.
Right arrow Articles by Gould, S. J.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 2000, p. 7516-7526, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

The Peroxisome Biogenesis Factors Pex4p, Pex22p, Pex1p, and Pex6p Act in the Terminal Steps of Peroxisomal Matrix Protein Import

Cynthia S. Collins,1 Jennifer E. Kalish,1 James C. Morrell,1 J. Michael McCaffery,2 and Stephen J. Gould1,*

Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205,1 and Integrated Imaging Center, Department of Biology, The Johns Hopkins University, Baltimore, Maryland 212182

Received 20 March 2000/Returned for modification 1 May 2000/Accepted 1 August 2000

Peroxisomes are independent organelles found in virtually all eukaryotic cells. Genetic studies have identified more than 20 PEX genes that are required for peroxisome biogenesis. The role of most PEX gene products, peroxins, remains to be determined, but a variety of studies have established that Pex5p binds the type 1 peroxisomal targeting signal and is the import receptor for most newly synthesized peroxisomal matrix proteins. The steady-state abundance of Pex5p is unaffected in most pex mutants of the yeast Pichia pastoris but is severely reduced in pex4 and pex22 mutants and moderately reduced in pex1 and pex6 mutants. We used these subphenotypes to determine the epistatic relationships among several groups of pex mutants. Our results demonstrate that Pex4p acts after the peroxisome membrane synthesis factor Pex3p, the Pex5p docking factors Pex13p and Pex14p, the matrix protein import factors Pex8p, Pex10p, and Pex12p, and two other peroxins, Pex2p and Pex17p. Pex22p and the interacting AAA ATPases Pex1p and Pex6p were also found to act after Pex10p. Furthermore, Pex1p and Pex6p were found to act upstream of Pex4p and Pex22p. These results suggest that Pex1p, Pex4p, Pex6p, and Pex22p act late in peroxisomal matrix protein import, after matrix protein translocation. This hypothesis is supported by the phenotypes of the corresponding mutant strains. As has been shown previously for P. pastoris pex1, pex6, and pex22 mutant cells, we show here that pex4Delta mutant cells contain peroxisomal membrane protein-containing peroxisomes that import residual amounts of peroxisomal matrix proteins.


* Corresponding author. Mailing address: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205. Phone: (410) 955-3424. Fax: (410) 955-0215. E-mail: sgould{at}jhmi.edu.


Molecular and Cellular Biology, October 2000, p. 7516-7526, Vol. 20, No. 20
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



This article has been cited by other articles:

  • Ma, C., Schumann, U., Rayapuram, N., Subramani, S. (2009). The Peroxisomal Matrix Import of Pex8p Requires Only PTS Receptors and Pex14p. Mol. Biol. Cell 20: 3680-3689 [Abstract] [Full Text]  
  • Mukherjee, D., Coon, B. G., Edwards, D. F. III, Hanna, C. B., Longhi, S. A., McCaffery, J. M., Wendland, B., Retegui, L. A., Bi, E., Aguilar, R. C. (2009). The yeast endocytic protein Epsin 2 functions in a cell-division signaling pathway. J. Cell Sci. 122: 2453-2463 [Abstract] [Full Text]  
  • Grou, C. P., Carvalho, A. F., Pinto, M. P., Wiese, S., Piechura, H., Meyer, H. E., Warscheid, B., Sa-Miranda, C., Azevedo, J. E. (2008). Members of the E2D (UbcH5) Family Mediate the Ubiquitination of the Conserved Cysteine of Pex5p, the Peroxisomal Import Receptor. J. Biol. Chem. 283: 14190-14197 [Abstract] [Full Text]  
  • Williams, C., van den Berg, M., Sprenger, R. R., Distel, B. (2007). A Conserved Cysteine Is Essential for Pex4p-dependent Ubiquitination of the Peroxisomal Import Receptor Pex5p. J. Biol. Chem. 282: 22534-22543 [Abstract] [Full Text]  
  • Platta, H. W., Magraoui, F. E., Schlee, D., Grunau, S., Girzalsky, W., Erdmann, R. (2007). Ubiquitination of the peroxisomal import receptor Pex5p is required for its recycling. JCB 177: 197-204 [Abstract] [Full Text]  
  • Leon, S., Subramani, S. (2007). A Conserved Cysteine Residue of Pichia pastoris Pex20p Is Essential for Its Recycling from the Peroxisome to the Cytosol. J. Biol. Chem. 282: 7424-7430 [Abstract] [Full Text]  
  • Leon, S., Zhang, L., McDonald, W. H., Yates, J. III, Cregg, J. M., Subramani, S. (2006). Dynamics of the peroxisomal import cycle of PpPex20p: ubiquitin-dependent localization and regulation. JCB 172: 67-78 [Abstract] [Full Text]  
  • Miyata, N., Fujiki, Y. (2005). Shuttling Mechanism of Peroxisome Targeting Signal Type 1 Receptor Pex5: ATP-Independent Import and ATP-Dependent Export. Mol. Cell. Biol. 25: 10822-10832 [Abstract] [Full Text]  
  • Zolman, B. K., Monroe-Augustus, M., Silva, I. D., Bartel, B. (2005). Identification and Functional Characterization of Arabidopsis PEROXIN4 and the Interacting Protein PEROXIN22. Plant Cell 17: 3422-3435 [Abstract] [Full Text]  
  • Schell-Steven, A., Stein, K., Amoros, M., Landgraf, C., Volkmer-Engert, R., Rottensteiner, H., Erdmann, R. (2005). Identification of a Novel, Intraperoxisomal Pex14-Binding Site in Pex13: Association of Pex13 with the Docking Complex Is Essential for Peroxisomal Matrix Protein Import. Mol. Cell. Biol. 25: 3007-3018 [Abstract] [Full Text]  
  • Kragt, A., Voorn-Brouwer, T., van den Berg, M., Distel, B. (2005). The Saccharomyces cerevisiae Peroxisomal Import Receptor Pex5p Is Monoubiquitinated in Wild Type Cells. J. Biol. Chem. 280: 7867-7874 [Abstract] [Full Text]  
  • Woodward, A. W., Bartel, B. (2005). The Arabidopsis Peroxisomal Targeting Signal Type 2 Receptor PEX7 Is Necessary for Peroxisome Function and Dependent on PEX5. Mol. Biol. Cell 16: 573-583 [Abstract] [Full Text]  
  • Kiel, J. A. K. W., Emmrich, K., Meyer, H. E., Kunau, W.-H. (2005). Ubiquitination of the Peroxisomal Targeting Signal Type 1 Receptor, Pex5p, Suggests the Presence of a Quality Control Mechanism during Peroxisomal Matrix Protein Import. J. Biol. Chem. 280: 1921-1930 [Abstract] [Full Text]  
  • Shiozawa, K., Maita, N., Tomii, K., Seto, A., Goda, N., Akiyama, Y., Shimizu, T., Shirakawa, M., Hiroaki, H. (2004). Structure of the N-terminal Domain of PEX1 AAA-ATPase: CHARACTERIZATION OF A PUTATIVE ADAPTOR-BINDING DOMAIN. J. Biol. Chem. 279: 50060-50068 [Abstract] [Full Text]  
  • Costa-Rodrigues, J., Carvalho, A. F., Gouveia, A. M., Fransen, M., Sa-Miranda, C., Azevedo, J. E. (2004). The N Terminus of the Peroxisomal Cycling Receptor, Pex5p, Is Required for Redirecting the Peroxisome-associated Peroxin Back to the Cytosol. J. Biol. Chem. 279: 46573-46579 [Abstract] [Full Text]  
  • Zolman, B. K., Bartel, B. (2004). An Arabidopsis indole-3-butyric acid-response mutant defective in PEROXIN6, an apparent ATPase implicated in peroxisomal function. Proc. Natl. Acad. Sci. USA 101: 1786-1791 [Abstract] [Full Text]  
  • Sparkes, I. A., Brandizzi, F., Slocombe, S. P., El-Shami, M., Hawes, C., Baker, A. (2003). An Arabidopsis pex10 Null Mutant Is Embryo Lethal, Implicating Peroxisomes in an Essential Role during Plant Embryogenesis. Plant Physiol. 133: 1809-1819 [Abstract] [Full Text]  
  • Oliveira, M. E., Gouveia, A. M., Pinto, R. A., Sa-Miranda, C., Azevedo, J. E. (2003). The Energetics of Pex5p-mediated Peroxisomal Protein Import. J. Biol. Chem. 278: 39483-39488 [Abstract] [Full Text]  
  • Birschmann, I., Stroobants, A. K., van den Berg, M., Schafer, A., Rosenkranz, K., Kunau, W.-H., Tabak, H. F. (2003). Pex15p of Saccharomyces cerevisiae Provides a Molecular Basis for Recruitment of the AAA Peroxin Pex6p to Peroxisomal Membranes. Mol. Biol. Cell 14: 2226-2236 [Abstract] [Full Text]  
  • Gouveia, A. M., Guimaraes, C. P., Oliveira, M. E., Reguenga, C., Sa-Miranda, C., Azevedo, J. E. (2003). Characterization of the Peroxisomal Cycling Receptor, Pex5p, Using a Cell-free in Vitro Import System. J. Biol. Chem. 278: 226-232 [Abstract] [Full Text]  
  • Fransen, M., Brees, C., Ghys, K., Amery, L., Mannaerts, G. P., Ladant, D., Van Veldhoven, P. P. (2002). Analysis of Mammalian Peroxin Interactions Using a Non-transcription-based Bacterial Two-hybrid Assay. Mol. Cell. Proteomics 1: 243-252 [Abstract] [Full Text]  
  • Purdue, P. E., Lazarow, P. B. (2001). Pex18p Is Constitutively Degraded during Peroxisome Biogenesis. J. Biol. Chem. 276: 47684-47689 [Abstract] [Full Text]  
  • Fransen, M., Wylin, T., Brees, C., Mannaerts, G. P., Van Veldhoven, P. P. (2001). Human Pex19p Binds Peroxisomal Integral Membrane Proteins at Regions Distinct from Their Sorting Sequences. Mol. Cell. Biol. 21: 4413-4424 [Abstract] [Full Text]  
  • Hashiguchi, N., Kojidani, T., Imanaka, T., Haraguchi, T., Hiraoka, Y., Baumgart, E., Yokota, S., Tsukamoto, T., Osumi, T. (2002). Peroxisomes Are Formed from Complex Membrane Structures in PEX6-deficient CHO Cells upon Genetic Complementation. Mol. Biol. Cell 13: 711-722 [Abstract] [Full Text]