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

Authors
Citation
G. Dodt et Sj. Gould, 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, 135(6), 1996, pp. 1763-1774
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell Biology
Journal title
ISSN journal
0021-9525
Volume
135
Issue
6
Year of publication
1996
Part
2
Pages
1763 - 1774
Database
ISI
SICI code
0021-9525(1996)135:6<1763:MPGARF>2.0.ZU;2-6
Abstract
PEX5 encodes the type-1 peroxisomal targeting signal (PTS1) receptor, one of at least 15 peroxins required for peroxisome biogenesis, Pex5p has a bi-modal distribution within the cell, mostly cytosolic with a s mall amount bound to peroxisomes. This distribution indicates that Pex 5p may function as a cycling receptor, a mode of action likely to requ ire interaction with additional peroxins. Loss of peroxins required fo r protein translocation into the peroxisome (PEX2 or PEX12) resulted i n accumulation of Pex5p at docking sites on the peroxisome surface. Pe x5p also accumulated on peroxisomes in normal cells under conditions w hich inhibit protein translocation into peroxisomes (low temperature o r ATP depletion), returned to the cytoplasm when translocation was res tored, and reaccumulated on peroxisomes when translocation was again i nhibited. Translocation inhibiting conditions did not result in Pex5p redistribution in cells that lack detectable peroxisomes. Thus, it app ears that Pex5p can cycle repeatedly between the cytoplasm and peroxis ome. Altered activity of the peroxin defective in CG7 cells leads to a ccumulation of Pex5p within the peroxisome, indicating that Pex5p may actually enter the peroxisome lumen at one point in its cycle. In addi tion, we found that the PTS1 receptor was extremely unstable in the pe roxin-deficient CG1, CG4, and CG8 cells, Altered distribution or stabi lity of the PTS1 receptor in all cells with a defect in PTS1 protein i mport implies that the genes mutated in these cell lines encode protei ns with a direct role in peroxisomal protein import.