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Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol

Nature Cell Biology volume 7, pages 817–822 (2005)Cite this article

Abstract

Peroxisomal import receptors bind their cargo proteins in the cytosol and target them to docking and translocation machinery at the peroxisomal membrane (reviewed in ref. 1). The receptors release the cargo proteins into the peroxisomal lumen and, according to the model of cycling receptors, they are supposed to shuttle back to the cytosol. This shuttling of the receptors has been assigned to peroxins including the AAA peroxins Pex1p and Pex6p, as well as the ubiquitin-conjugating enzyme Pex4p (reviewed in ref. 2). One possible target for Pex4p is the PTS1 receptor Pex5p, which has recently been shown to be ubiquitinated3,4,5. Pex1p and Pex6p are both cytosolic and membrane-associated AAA ATPases of the peroxisomal protein import machinery, the exact function of which is still unknown. Here we demonstrate that the AAA peroxins mediate the ATP-dependent dislocation of the peroxisomal targeting signal-1 (PTS1) receptor from the peroxisomal membrane to the cytosol.

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Figure 1: Pex5p forms a complex with the AAA group peroxins and accumulates at the peroxisomal membrane in their absence.
Figure 2: In vitro export assays and localization studies of Pex5p.
Figure 3: The AAA peroxins dislocate Pex5p from the peroxisomal membrane to the cytosol.
Figure 4: Cycling of the PTS1 receptor Pex5p between the peroxisomal membrane and the cytosol.

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Acknowledgements

We are grateful to U. Ricken for technical assistance. We thank C. Mann for kindly providing the cim5-1 strain and we are grateful to W.-H. Kunau, W. Schliebs and M. Witt-Reinhardt for the reading of the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (SFB480, SFB642), the FP6 European Union Project 'Peroxisome' (LSHG–CT-2004–512018) and by the Fonds der Chemischen Industrie.

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  1. Harald W. Platta and Silke Grunau: These authors contributed equally to this work.

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  1. Institut für Physiologische Chemie, Abt. Systembiochemie, Ruhr-Universität Bochum, Bochum, D-44780, Germany

    Harald W. Platta, Silke Grunau, Katja Rosenkranz, Wolfgang Girzalsky & Ralf Erdmann

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Platta, H., Grunau, S., Rosenkranz, K. et al. Functional role of the AAA peroxins in dislocation of the cycling PTS1 receptor back to the cytosol. Nat Cell Biol 7, 817–822 (2005). https://doi.org/10.1038/ncb1281

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