The Mammalian Peroxin Pex5pL, the Longer Isoform of the Mobile Peroxisome Targeting Signal (PTS) Type 1 Transporter, Translocates the Pex7p·PTS2 Protein Complex into Peroxisomes via Its Initial Docking Site, Pex14p

Abstract

In mammals, two isoforms of the peroxisome targeting signal (PTS) type 1 receptor Pex5p, i.e. Pex5pS and Pex5pL with an internal 37-amino acid insertion, have previously been identified. Expression of either type of Pex5p complements the impaired PTS1 import in Chinese hamster ovary pex5 mutants, but only Pex5pL can rescue the PTS2 import defect noted in a subgroup of pex5 mutants such as ZP105. In this work, we found that Pex5pL directly interacts with the PTS2 receptor Pex7p, carrying its cargo PTS2 protein in the cytosol. Pex5pL, but not Pex5pS, mediated the binding of PTS2 protein to Pex14p by translocating Pex7p, demonstrating that Pex5pL plays a pivotal role in peroxisomal PTS2 import. Pex5p was localized mostly in the cytosol in wild-type CHO-K1 and Pex14p-deficient mutant cells, whereas it accumulated in the peroxisomal remnants in cell mutants defective in Pex13p or the RING family peroxins such as Pex2p and Pex12p. Furthermore, overexpression of Pex14p, but not Pex10p, Pex12p, or Pex13p, caused accumulation of Pex5p in peroxisomal membranes, with concomitant interference with PTS1 and PTS2 import. Therefore, Pex5p carrying the cargoes most likely docks with the initial site (Pex14p) in a putative import machinery, subsequently translocating to other components such as Pex13p, Pex2p, Pex10p, and Pex12p.

A Novel Fluorescent Sensor Protein for Visualization of Redox States in the Cytoplasm and in Peroxisomes

“…The import of catalase was not restored in ZP105 cells following culture at 30°C for 7 days, which is reminiscent of the phenotype of infant Refsum disease, a milder form of PBD (Fig. 5B) (26). These results suggest that mislocalization of peroxisomal catalase is not the main cause of abnormal reductive states observed in cells mutant for peroxisome assembly.…”

Yarrowia lipolyticaCells Mutant for the Peroxisomal Peroxin Pex19p Contain Structures Resembling Wild-Type Peroxisomes

“…Pex5p and Pex7p are the receptors for PTS1 and PTS2, respectively, and various peroxins, including Pex13p and Pex14p, form a docking complex at the peroxisomal membrane for these receptors (reviewed by Erdmann et al, 1997;Subramani, 1998Titorenko and Rachubinski, 2001). The PTS1 and PTS2 pathways are apparently not independent, because there is convergence of the two targeting pathways either in the cytosol or at the level of the peroxisomal membrane (Fransen et al, 1998;Otera et al, 1998Otera et al, , 2000Schliebs et al, 1999). The sorting of peroxisomal membrane proteins is much less well understood than the sorting of matrix proteins, although it appears that the two pathways are independent.…”

Peroxisomal Targeting Signal Receptor Pex5p Interacts with Cargoes and Import Machinery Components in a Spatiotemporally Differentiated Manner: Conserved Pex5p WXXXF/Y Motifs Are Critical for Matrix Protein Import

“…PEX5 and PEX7 encode the receptors for PTS1 and PTS2, respectively. Of note, catalase with the Cterminal sequence KANL is also imported into peroxisomes by the Pex5p-dependent pathway (29,32). However, the underlying molecular mechanism for catalase import remains unclear.…”