title: A cargo-centered perspective on the PEX5 receptor-mediated peroxisomal protein import pathway.
abstract: Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and post-translationally targeted to the organelle by PEX5, the peroxisomal shuttling receptor. The pathway followed by PEX5 during this process is known with reasonable detail. After recognizing cargo proteins in the cytosol, the receptor interacts with the peroxisomal docking/translocation machinery, where it gets inserted; PEX5 is then monoubiquitinated, extracted back to the cytosol and, finally, deubiquitinated. However, despite this information, the exact step of this pathway where cargo proteins are translocated across the organelle membrane is still ill-defined. In this work, we used an in vitro import system to characterize the translocation mechanism of a matrix protein possessing a type 1 targeting signal. Our results suggest that translocation of proteins across the organelle membrane occurs downstream of a reversible docking step and upstream of the first cytosolic ATP-dependent step (i.e. before ubiquitination of PEX5), concomitantly with the insertion of the receptor into the docking/translocation machinery.
authors: From the Organelle Biogenesis and Function Group and.
authors: Tânia
authors: T
authors: Francisco
authors: Tony A
authors: TA
authors: Rodrigues
authors: Marta O
authors: MO
authors: Freitas
authors: Cláudia P
authors: CP
authors: Grou
authors: Andreia F
authors: AF
authors: Carvalho
authors: Clara
authors: C
authors: Sá-Miranda
authors: Manuel P
authors: MP
authors: Pinto
authors: Jorge E
authors: JE
authors: Azevedo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000378:metabolism*; D021382:Protein Sorting Signals; D021381:Protein Transport; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D013696:Temperature
chemical_list: D002352:Carrier Proteins; C000614264:PEX5 protein, human; D000074435:Peroxisome-Targeting Signal 1 Receptor; C000614265:Pex5 protein, mouse; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear; C072087:sterol carrier proteins; D000255:Adenosine Triphosphate
keywords: In Vitro Import Assays; PEX5; PTS1 Protein; Peroxisomes; Protein Sorting; Protein Translocation; Subcellular Organelles; Ubiquitination
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