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The peroxisomal importomer constitutes a large and highly dynamic pore

Nature Cell Biology volume 12, pages 273–277 (2010)Cite this article

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Abstract

The peroxisomal protein import machinery differs fundamentally from known translocons (endoplasmic reticulum, mitochondria, chloroplasts, bacteria) as it allows membrane passage of folded, even oligomerized proteins1. However, the mechanistic principles of protein translocation across the peroxisomal membrane remain unknown. There are various models that consider membrane invagination events, vesicle fusion or the existence of large import pores. Current data show that a proteinaceous peroxisomal importomer enables docking of the cytosolic cargo-loaded receptors, cargo translocation and receptor recycling2. Remarkably, the cycling import receptor Pex5p changes its topology from a soluble cytosolic form to an integral membrane-bound form. According to the transient pore hypothesis, the membrane-bound receptor is proposed to form the core component of the peroxisomal import pore3. Here, we demonstrate that the membrane-associated import receptor Pex5p together with its docking partner Pex14p forms a gated ion-conducting channel which can be opened to a diameter of about 9 nm by the cytosolic receptor–cargo complex. The newly identified pore shows striking dynamics, as expected for an import machinery translocating proteins of variable sizes.

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Figure 1: Identification, purification and composition of a Pex5p-containing sub-complex with ion channel activity.
Figure 2: Characterization of the electrophysiological properties of the peroxisomal import pore and receptor/cargo dependent activation.
Figure 3: Analysis of gating connectivity of the activated peroxisomal import pore.
Figure 4: The transient translocation pore in the current view of receptor-cycle-mediated protein import into peroxisomes.

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Acknowledgements

This work was supported by grants from the Deutsche Forschungsgemeinschaft SFB431 (M.M. and R.W.), SFB642 (R.E.), DFGSchl 584/1-2 (WS) and the Fonds der Chemischen Industrie. We thank Wolf Kunau for helpful comments and discussion.

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Author notes

  1. Michael Meinecke

    Present address: Current address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.,

  2. Michael Meinecke, Christian Cizmowski and Wolfgang Schliebs: These authors contributed equally to this work.

Authors and Affiliations

  1. Biophysik, FB Biologie/Chemie, Universität Osnabrück, Germany

    Michael Meinecke, Vivien Krüger & Richard Wagner

  2. Institut für Physiologische Chemie, Ruhr-Universität Bochum, Germany

    Christian Cizmowski, Wolfgang Schliebs, Sabrina Beck & Ralf Erdmann

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  1. Michael Meinecke
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Contributions

M.M. and V.K. performed all electrophysiological measurements and analysed data; C.C. and S.B. prepared and analysed the samples and reconstituted them into proteoliposomes; M.M., W.S., R.W. and R.E. designed the study and wrote the manuscript.

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Correspondence to Ralf Erdmann.

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Meinecke, M., Cizmowski, C., Schliebs, W. et al. The peroxisomal importomer constitutes a large and highly dynamic pore. Nat Cell Biol 12, 273–277 (2010). https://doi.org/10.1038/ncb2027

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