The human peroxisomal targeting signal receptor, Pex5p, is translocated into the peroxisomal matrix and recycled to the cytosol.
Peroxisomal targeting signals (PTSs) are recognized by predominantly cytosolic receptors, Pex5p and Pex7p. The fate of these PTS receptors following their interactions on the peroxisomal membrane with components of docking and putative translocation complexes is unknown. Using both novel and multiple experimental approaches, we show that human Pex5p does not just bind cargo and deliver it to the peroxisome membrane, but participates in multiple rounds of entry into the peroxisome matrix and export to the cytosol independent of the PTS2 import pathway. This unusual shuttling mechanism for the PTS1 receptor distinguishes protein import into peroxisomes from that into most other organelles, with the exception of the nucleus.
Dammai
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Section of Molecular Biology, Division of Biology, Room 3230 Bonner Hall, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Subramani
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D002458:Cell Fractionation; D002460:Cell Line; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D004072:Digitonin / Q000494:pharmacology; D010450:Endopeptidases / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D015151:Immunoblotting; D007202:Indicators and Reagents / Q000494:pharmacology; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D003902:Detergents; D007202:Indicators and Reagents; D008565:Membrane Proteins; D000074435:Peroxisome-Targeting Signal 1 Receptor; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; C085380:peroxisomal targeting sequence receptor; D017830:Octoxynol; D010450:Endopeptidases; D004072:Digitonin