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

• Published in: Communications biology 2021-03, Vol.4 (1), p.336-336, Article 336
• Main Authors: Hitz, Eva, Grüninger, Olivia, Passecker, Armin, Wyss, Matthias, Scheurer, Christian, Wittlin, Sergio, Beck, Hans-Peter, Brancucci, Nicolas M. B., Voss, Till S.
• Format: Article
• Language: English
• Subjects: 13/1; 13/109; 13/31; 13/44; 14/1; 14/35; 14/63; 38/70; 38/77; 42/41; 631/326/417/1716; 631/326/417/2549; 631/326/417/2550; 631/337/4041/3196; Antimalarials - pharmacology; Asexuality; Biology; Biomedical and Life Sciences; Blood; Casein; Casein kinase II; Casein Kinase II - antagonists & inhibitors; Casein Kinase II - genetics; Casein Kinase II - metabolism; Catalytic Domain; CRISPR; CRISPR-Cas Systems; Cytoplasm; Disease transmission; Erythrocytes; Erythrocytes - parasitology; Gametocytes; Gametogenesis; Gene Editing; Humans; Kinases; Life Cycle Stages; Life Sciences; Malaria; Parasites; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium falciparum - growth & development; Plasmodium falciparum - metabolism; Protein kinase; Protein Kinase Inhibitors - pharmacology; Protozoan Proteins - genetics; Protozoan Proteins - metabolism; Reproduction, Asexual; Sex differentiation
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-01873-0

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. Hitz et al. describe the role of the protein kinase PfCK2α in the development of the human malaria parasite Plasmodium falciparum . Using mutant parasites, they show that PfCK2α is not only essential for asexual but also sexual development of P. falciparum blood stage parasites, and hence it may hold promise as a potential target for antimalarial drugs.