Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny
In: Cellular and Molecular Life Sciences Cellular and Molecular Life Sciences, 2018, 75 (23), pp.4417-4443. ⟨10.1007/s00018-018-2889-6⟩ Cellular and Molecular Life Sciences, Springer Verlag, 2018, 75 (23), pp.4417-4443. ⟨10.1007/s00018-018-2889-6⟩; (2018)
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Zugriff:
The phylum Apicomplexa encompasses deadly pathogens such as malaria and Cryptosporidium. Apicomplexa cell division is mechanistically divergent from that of their mammalian host, potentially representing an attractive source of drug targets. Depending on the species, apicomplexan parasites can modulate the output of cell division, producing two to thousands of daughter cells at once. The inherent flexibility of their cell division mechanisms allows these parasites to adapt to different niches, facilitating their dissemination. Toxoplasma gondii tachyzoites divide using a unique form of cell division called endodyogeny. This process involves a single round of DNA replication, closed nuclear mitosis, and assembly of two daughter cells within a mother. In higher Eukaryotes, the four-subunit chromosomal passenger complex (CPC) (Aurora kinase B (ARKB)/INCENP/Borealin/Survivin) promotes chromosome bi-orientation by detaching incorrect kinetochore-microtubule attachments, playing an essential role in controlling cell division fidelity. Herein, we report the characterization of the Toxoplasma CPC (Aurora kinase 1 (Ark1)/INCENP1/INCENP2). We show that the CPC exhibits dynamic localization in a cell cycle-dependent manner. TgArk1 interacts with both TgINCENPs, with TgINCENP2 being essential for its translocation to the nucleus. While TgINCENPl appears to be dispensable, interfering with TgArk1 or TgINCENP2 results in pronounced division and growth defects. Significant anti-cancer drug development efforts have focused on targeting human ARKB. Parasite treatment with low doses of hesperadin, a known inhibitor of human ARKB at higher concentrations, phenocopies the TgArk1 and TgINCENP2 mutants. Overall, our study provides new insights into the mechanisms underpinning cell cycle control in Apicomplexa, and highlights TgArk1 as potential drug target.
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Toxoplasma gondii chromosomal passenger complex is essential for the organization of a functional mitotic spindle: a prerequisite for productive endodyogeny
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Autor/in / Beteiligte Person: | Bordat, Yann ; Morlon-Guyot, Juliette ; Daher, Wassim ; Chen, Chun-Ti ; Saliou, Jean-Michel ; Grandmougin, Maurane ; Lebrun, Maryse ; Francia, Maria E. ; Berry, Laurence ; Guérin, Amandine ; Wein, Sharon ; Graindorge, Arnault ; Gubbels, Marc-Jan ; Bechara, Cherine ; Dubremetz, Jean-François ; Dynamique des interactions membranaires normales et pathologiques (DIMNP) ; Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) ; Institut de Génomique Fonctionnelle (IGF) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS) ; Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL) ; Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS) ; Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1) ; Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS) ; Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille ; Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP) |
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Quelle: | Cellular and Molecular Life Sciences Cellular and Molecular Life Sciences, 2018, 75 (23), pp.4417-4443. ⟨10.1007/s00018-018-2889-6⟩ Cellular and Molecular Life Sciences, Springer Verlag, 2018, 75 (23), pp.4417-4443. ⟨10.1007/s00018-018-2889-6⟩; (2018) |
Veröffentlichung: | HAL CCSD, 2018 |
Medientyp: | unknown |
ISSN: | 1420-682X (print) ; 1420-9071 (print) |
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