Functional analyses of a putative, membrane-bound, peroxisomal protein import mechanism from the apicomplexan protozoan Toxoplasma gondii

Mbekeani, A. J., Stanley, W. A., Kalel, V. C., Dahan, N., Zalckvar, E., Sheiner, L. , Schliebs, W., Erdmann, R., Pohl, E. and Denny, P. W. (2018) Functional analyses of a putative, membrane-bound, peroxisomal protein import mechanism from the apicomplexan protozoan Toxoplasma gondii. Genes, 9(9), 434. (doi: 10.3390/genes9090434) (PMID:30158461) (PMCID:PMC6162456)

Abstract

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 was shown to rescue the import defect of Pex5-deleted . 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 Furthermore, the PTS1-binding domain of Pex5 and a PTS1 ligand from the putatively peroxisome-localised 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.

• Item Type: Articles
• Additional Information: This work was supported by the Biotechnology and Biological Research Council (BB/M024156/1 to P.W.D. and E.P.), FoRUM Grants of the Ruhr-University Bochum (F883-2016 and F913-2017 to V.C.K.,W.S. and R.E.) and a Durham Biophysical Sciences Pump Priming award (to P.W.D.). A.J.M. benefited from a British Society for Parasitology International Training and Fieldwork Award which part supported her research secondment at Ruhr University Bochum. L.S. is a Royal Society of Edinburgh Fellow.
• Keywords: Apicomplexa, Pex5, Toxoplasma, peroxin, peroxisomes.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sheiner, Professor Lilach
• Authors: Mbekeani, A. J., Stanley, W. A., Kalel, V. C., Dahan, N., Zalckvar, E., Sheiner, L., Schliebs, W., Erdmann, R., Pohl, E., and Denny, P. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Genes
• Publisher: MDPI
• ISSN: 2073-4425
• ISSN (Online): 2073-4425
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Genes 9(9):434
• Publisher Policy: Reproduced under a Creative Commons License