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PMID: 8991089 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

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.

The Journal of cell biology ·Vol. 135 ·No. 6 Pt 2 ·1996-12-00 ·Pages 1763-74

Dodt G, Gould SJ

Abstract

PEX5 encodes the type-1 peroxisomal targeting signal (PTS1) receptor, one of at least 15 peroxins required for peroxisome biogenesis. Pex5p has a bimodal distribution within the cell, mostly cytosolic with a small amount bound to peroxisomes. This distribution indicates that Pex5p may function as a cycling receptor, a mode of action likely to require interaction with additional peroxins. Loss of peroxins required for protein translocation into the peroxisome (PEX2 or PEX12) resulted in accumulation of Pex5p at docking sites on the peroxisome surface. Pex5p also accumulated on peroxisomes in normal cells under conditions which inhibit protein translocation into peroxisomes (low temperature or ATP depletion), returned to the cytoplasm when translocation was restored, and reaccumulated on peroxisomes when translocation was again inhibited. Translocation inhibiting conditions did not result in Pex5p redistribution in cells that lack detectable peroxisomes. Thus, it appears that Pex5p can cycle repeatedly between the cytoplasm and peroxisome. Altered activity of the peroxin defective in CG7 cells leads to accumulation of Pex5p within the peroxisome, indicating that Pex5p may actually enter the peroxisome lumen at one point in its cycle. In addition, we found that the PTS1 receptor was extremely unstable in the peroxin-deficient CG1, CG4, and CG8 cells. Altered distribution or stability of the PTS1 receptor in all cells with a defect in PTS1 protein import implies that the genes mutated in these cell lines encode proteins with a direct role in peroxisomal protein import.

MeSH Terms
Biological Transport/physiology Cell Compartmentation/physiology Cell Line/chemistry,physiology,ultrastructure Cytoplasm/metabolism Fibroblasts/chemistry,physiology,ultrastructure Fluorescent Antibody Technique Humans Microbodies/metabolism Peroxisome-Targeting Signal 1 Receptor Receptors, Cytoplasmic and Nuclear/analysis,genetics,metabolism Skin/cytology Subcellular Fractions/chemistry
Chemicals
PEX5 protein, human Peroxisome-Targeting Signal 1 Receptor Receptors, Cytoplasmic and Nuclear
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Dodt G
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Gould S J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.135.6.1763
Published
1996-12-00
Pages
1763-74
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2133940
Subset
IM
Grants
NIDDK NIH HHS · DK45787 · United States
External Links
PubMed source DOI: 10.1083/jcb.135.6.1763 PMC Full Text View journal details
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