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Direct evidence of O-GlcNAcylation in the apicomplexan Toxoplasma gondii: a biochemical and bioinformatic study

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Abstract

Toxoplasma gondii and Plasmodium falciparum are apicomplexan parasites responsible for serious diseases in humans. Many studies have focused on the post-translational modifications (PTMs) found in the two protists including phosphorylation, acetylation or SUMOylation but only a few of these are concerned with the nuclear and cytosolic-specific glycosylation O-GlcNAcylation. O-GlcNAcylation is a highly dynamic PTM—regulated by the ON and OFF enzymes: O-GlcNAc transferase and O-GlcNAcase—that can compete with phosphorylation but its function remains unclear. In this work, we directly prove the O-GlcNAcylation in T. gondii using antibodies specifically directed against the modification and we strongly suggest its occurrence in P. falciparum. We found that the inducible 70 kDa-Heat Shock Protein is O-GlcNAcylated, or associated with an O-GlcNAc-partner, in T. gondii. Using anti-OGT antibodies we were able to detect the expression of the glycosyltransferase in T. gondii cultured both in human foreskin fibroblast and in Vero cells and report its putative sequence. For the first time the presence of O-GlcNAcylation is unequivocally shown in T. gondii and suspected in P. falciparum. Since the O-GlcNAcylation is implicated in many biological fundamental processes this study opens a new research track in the knowledge of apicomplexans’ life cycle and pathogenic potential.

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Acknowledgments

We thank the “Université de Lille 1” (Villeneuve d’Ascq, France) and the “Centre National de la Recherche Scientifique” and the “Deutsche Forschungsgemeinschaft” (Bonn, Germany). We are particularly grateful to Professor Gerald W. Hart for the kind gift of AL25, AL35 and CTD110.6. YPC is a recipient of a Rosalind Franklin fellowship.

Conflict of interest

The authors declare that they have no conflict of interest.

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Author notes

  1. Vanessa Dehennaut

    Present address: CNRS-UMR 8161, Genetic, Functional and Structural Approaches of Cancers, Institut de Biologie de LILLE, IFR 142, Universités de LILLE 1 et de LILLE 2, Institut PASTEUR de LILLE, 1, Rue Calmette, BP 447, 59021, Lille Cedex, France

Authors and Affiliations

  1. Unit of Structural and Functional Glycobiology, CNRS-UMR 8576, IFR 147, Université de Lille 1, Cité Scientifique, 59655, Villeneuve d’Ascq, France

    Yobana Perez-Cervera, Grégoire Harichaux, Vanessa Dehennaut, Edwige Meurice, Tony Lefebvre & Ralph T. Schwarz

  2. Institut für Virologie, AG Parasitologie, Philipps University Marburg, Hans-Meerwein-Str. 2, 35043, Marburg, Germany

    Jörg Schmidt, Françoise Debierre-Grockiego, Ulrike Bieker & Ralph T. Schwarz

  3. UMR Université-INRA 0483, “Immunologie parasitaire, vaccinologie, biothérapies anti-infectieuses”, UFR Sciences Pharmaceutiques, 31 avenue Monge, 37200, Tours, France

    Françoise Debierre-Grockiego

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  1. Yobana Perez-Cervera
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  2. Grégoire Harichaux
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Corresponding author

Correspondence to Tony Lefebvre.

Additional information

Y. Perez-Cervera and G. Harichaux equally contribute together; T. Lefebvre and R. T. Schwarz equally contribute together.

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Perez-Cervera, Y., Harichaux, G., Schmidt, J. et al. Direct evidence of O-GlcNAcylation in the apicomplexan Toxoplasma gondii: a biochemical and bioinformatic study. Amino Acids 40, 847–856 (2011). https://doi.org/10.1007/s00726-010-0702-4

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