Cysteine-specific ubiquitination protects the peroxisomal import receptor Pex5p against proteasomal degradation

Schwartzkopff, Benjamin; Platta, Harald W.; Hasan, Sharizal; Girzalsky, Wolfgang; Erdmann, Ralf

doi:10.1042/bsr20150103

Cited by 30 publications

(26 citation statements)

References 73 publications

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“…Better understanding of the receptor export cycle has led to an appreciation that the import and export processes must be coupled, and that the ATP-dependent export process is necessary to remove PEX5 from the translocation pore [ 63 ] to facilitate further rounds of import. Mutation of the cysteine required for ubiquitination of S. cerevisiae PEX5 inhibits receptor export and blocks subsequent import which is consistent with this proposal [ 64 ]. A recently developed methodology in our laboratory that allows interrogation of protein–protein interactions during in vitro import of proteins into peroxisomes has also provided evidence consistent with export-coupled import [ 65 ].…”

Section: Export Coupled Importsupporting

confidence: 85%

Peroxisome protein import: a complex journey

Baker

Lanyon‐Hogg

Warriner

2016

Biochemical Society Transactions

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The import of proteins into peroxisomes possesses many unusual features such as the ability to import folded proteins, and a surprising diversity of targeting signals with differing affinities that can be recognized by the same receptor. As understanding of the structure and function of many components of the protein import machinery has grown, an increasingly complex network of factors affecting each step of the import pathway has emerged. Structural studies have revealed the presence of additional interactions between cargo proteins and the PEX5 receptor that affect import potential, with a subtle network of cargo-induced conformational changes in PEX5 being involved in the import process. Biochemical studies have also indicated an interdependence of receptor–cargo import with release of unloaded receptor from the peroxisome. Here, we provide an update on recent literature concerning mechanisms of protein import into peroxisomes.

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Section: Export Coupled Importsupporting

confidence: 85%

Peroxisome protein import: a complex journey

Baker

Lanyon‐Hogg

Warriner

2016

Biochemical Society Transactions

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“…For transformation, yeast were grown to exponential phase and transformed as previously described [ 25 , 26 , 27 , 28 , 29 , 30 ]. Single or double transformants were selected on −Ura or −Ura−Leu plates, respectively, and later cultured in selective liquid media containing 0.3% ( w / v ) glucose or 0.1% ( w / v ) oleic acid as previously described [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii

Mbekeani

Stanley

Kalel

et al. 2018

Genes

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Peroxisomes are central to eukaryotic metabolism, including the oxidation of fatty acids—which subsequently provide an important source of metabolic energy—and in the biosynthesis of cholesterol and plasmalogens. However, the presence and nature of peroxisomes in the parasitic apicomplexan protozoa remains controversial. A survey of the available genomes revealed that genes encoding peroxisome biogenesis factors, so-called peroxins (Pex), are only present in a subset of these parasites, the coccidia. The basic principle of peroxisomal protein import is evolutionarily conserved, proteins harbouring a peroxisomal-targeting signal 1 (PTS1) interact in the cytosol with the shuttling receptor Pex5 and are then imported into the peroxisome via the membrane-bound protein complex formed by Pex13 and Pex14. Surprisingly, whilst Pex5 is clearly identifiable, Pex13 and, perhaps, Pex14 are apparently absent from the coccidian genomes. To investigate the functionality of the PTS1 import mechanism in these parasites, expression of Pex5 from the model coccidian Toxoplasma gondii was shown to rescue the import defect of Pex5-deleted Saccharomyces cerevisiae. In support of these data, green fluorescent protein (GFP) bearing the enhanced (e)PTS1 known to efficiently localise to peroxisomes in yeast, localised to peroxisome-like bodies when expressed in Toxoplasma. Furthermore, the PTS1-binding domain of Pex5 and a PTS1 ligand from the putatively peroxisome-localised Toxoplasma sterol carrier protein (SCP2) were shown to interact in vitro. Taken together, these data demonstrate that the Pex5–PTS1 interaction is functional in the coccidia and indicate that a nonconventional peroxisomal import mechanism may operate in the absence of Pex13 and Pex14.

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“…cytosolic) Ub-PEX5 ends up in the ubiquitin-proteasome pathway. Data supporting both possibilities have been provided recently [105,106]. Second, monoubiquitination of PEX5 at the DTM is an integral and mandatory step of the PEX5 peroxisome-cytosol cycle, and not the result of some regulatory event occurring at the PIM [103,104,107,108].…”

Section: Disassembling the Syringe à Recycling Of Receptorsmentioning

confidence: 97%

Protein transport into peroxisomes: Knowns and unknowns

et al. 2017

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Peroxisomal matrix proteins are synthesized on cytosolic ribosomes and rapidly transported into the organelle by a complex machinery. The data gathered in recent years suggest that this machinery operates through a syringe-like mechanism, in which the shuttling receptor PEX5 - the "plunger" - pushes a newly synthesized protein all the way through a peroxisomal transmembrane protein complex - the "barrel" - into the matrix of the organelle. Notably, insertion of cargo-loaded receptor into the "barrel" is an ATP-independent process, whereas extraction of the receptor back into the cytosol requires its monoubiquitination and the action of ATP-dependent mechanoenzymes. Here, we review the main data behind this model.

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Cysteine-specific ubiquitination protects the peroxisomal import receptor Pex5p against proteasomal degradation

Cited by 30 publications

References 73 publications

Peroxisome protein import: a complex journey

Peroxisome protein import: a complex journey

Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii

Protein transport into peroxisomes: Knowns and unknowns

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