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Biochim Biophys Acta Mol Cell Res. 2019 Feb;1866(2):199-213. doi: 10.1016/j.bbamcr.2018.11.002. Epub 2018 Nov 6.

The deubiquitination of the PTS1-import receptor Pex5p is required for peroxisomal matrix protein import.

Author information

1
Biomedizinische Forschung, Leibniz-Insitute for Analytische Wissenschaften - ISAS e.V. - (ISAS e.V.), 44139 Dortmund, Germany; Systembiochemie, Ruhr-Universität Bochum, 44801 Bochum, Germany.
2
Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, 44801 Bochum, Germany.
3
Systembiochemie, Ruhr-Universität Bochum, 44801 Bochum, Germany.
4
Biomedizinische Forschung, Leibniz-Insitute for Analytische Wissenschaften - ISAS e.V. - (ISAS e.V.), 44139 Dortmund, Germany.
5
Functional Proteomics, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany.
6
Biochemie Intrazellulärer Transportprozesse, Ruhr-Universität Bochum, 44801 Bochum, Germany. Electronic address: Harald.Platta@rub.de.

Abstract

Peroxisomal biogenesis depends on the correct import of matrix proteins into the lumen of the organelle. Most peroxisomal matrix proteins harbor the peroxisomal targeting-type 1 (PTS1), which is recognized by the soluble PTS1-receptor Pex5p in the cytosol. Pex5p ferries the PTS1-proteins to the peroxisomal membrane and releases them into the lumen. Finally, the PTS1-receptor is monoubiquitinated on the conserved cysteine 6 in Saccharomyces cerevisiae. The monoubiquitinated Pex5p is recognized by the peroxisomal export machinery and is retrotranslocated into the cytosol for further rounds of protein import. However, the functional relevance of deubiquitination has not yet been addressed. In this study, we have analyzed a Pex5p-truncation lacking Cys6 [(Δ6)Pex5p], a construct with a ubiquitin-moiety genetically fused to the truncation [Ub-(Δ6)Pex5p], as well as a construct with a reduced susceptibility to deubiquitination [Ub(G75/76A)-(Δ6)Pex5p]. While the (Δ6)Pex5p-truncation is not functional, the Ub-(Δ6)Pex5p chimeric protein can facilitate matrix protein import. In contrast, the Ub(G75/76A)-(Δ6)Pex5p chimera exhibits a complete PTS1-import defect. The data show for the first time that not only ubiquitination but also deubiquitination rates are tightly regulated and that efficient deubiquitination of Pex5p is essential for peroxisomal biogenesis.

KEYWORDS:

Deubiquitination; Peroxisomes; Pex5p; Protein transport; Receptor; Ubiquitin

PMID:
30408545
DOI:
10.1016/j.bbamcr.2018.11.002
[Indexed for MEDLINE]
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