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The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis

Casein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate...

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Autores principales: Hitz, Eva, Grüninger, Olivia, Passecker, Armin, Wyss, Matthias, Scheurer, Christian, Wittlin, Sergio, Beck, Hans-Peter, Brancucci, Nicolas M. B., Voss, Till S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954856/
https://www.ncbi.nlm.nih.gov/pubmed/33712726
http://dx.doi.org/10.1038/s42003-021-01873-0
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author Hitz, Eva
Grüninger, Olivia
Passecker, Armin
Wyss, Matthias
Scheurer, Christian
Wittlin, Sergio
Beck, Hans-Peter
Brancucci, Nicolas M. B.
Voss, Till S.
author_facet Hitz, Eva
Grüninger, Olivia
Passecker, Armin
Wyss, Matthias
Scheurer, Christian
Wittlin, Sergio
Beck, Hans-Peter
Brancucci, Nicolas M. B.
Voss, Till S.
author_sort Hitz, Eva
collection PubMed
description Casein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate the function of the PfCK2α catalytic subunit in gametocytes, the sexual forms of the parasite that are essential for malaria transmission. We show that PfCK2α localizes to the nucleus and cytoplasm in asexual and sexual parasites alike. Conditional knockdown of PfCK2α expression prevented the transition of stage IV into transmission-competent stage V gametocytes, whereas the conditional knockout of pfck2a completely blocked gametocyte maturation already at an earlier stage of sexual differentiation. In summary, our results demonstrate that PfCK2α is not only essential for asexual but also sexual development of P. falciparum blood-stage parasites and encourage studies exploring PfCK2α as a potential target for dual-active antimalarial drugs.
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spelling pubmed-79548562021-03-28 The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis Hitz, Eva Grüninger, Olivia Passecker, Armin Wyss, Matthias Scheurer, Christian Wittlin, Sergio Beck, Hans-Peter Brancucci, Nicolas M. B. Voss, Till S. Commun Biol Article Casein kinase 2 (CK2) is a pleiotropic kinase phosphorylating substrates in different cellular compartments in eukaryotes. In the malaria parasite Plasmodium falciparum, PfCK2 is vital for asexual proliferation of blood-stage parasites. Here, we applied CRISPR/Cas9-based gene editing to investigate the function of the PfCK2α catalytic subunit in gametocytes, the sexual forms of the parasite that are essential for malaria transmission. We show that PfCK2α localizes to the nucleus and cytoplasm in asexual and sexual parasites alike. Conditional knockdown of PfCK2α expression prevented the transition of stage IV into transmission-competent stage V gametocytes, whereas the conditional knockout of pfck2a completely blocked gametocyte maturation already at an earlier stage of sexual differentiation. In summary, our results demonstrate that PfCK2α is not only essential for asexual but also sexual development of P. falciparum blood-stage parasites and encourage studies exploring PfCK2α as a potential target for dual-active antimalarial drugs. Nature Publishing Group UK 2021-03-12 /pmc/articles/PMC7954856/ /pubmed/33712726 http://dx.doi.org/10.1038/s42003-021-01873-0 Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hitz, Eva
Grüninger, Olivia
Passecker, Armin
Wyss, Matthias
Scheurer, Christian
Wittlin, Sergio
Beck, Hans-Peter
Brancucci, Nicolas M. B.
Voss, Till S.
The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
title The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
title_full The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
title_fullStr The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
title_full_unstemmed The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
title_short The catalytic subunit of Plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
title_sort catalytic subunit of plasmodium falciparum casein kinase 2 is essential for gametocytogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954856/
https://www.ncbi.nlm.nih.gov/pubmed/33712726
http://dx.doi.org/10.1038/s42003-021-01873-0
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