Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages

Zeeshan, Mohammad; Pandey, Rajan; Subudhi, Amit Kumar; Ferguson, David J.P.; Kaur, Gursimran; Rashpa, Ravish; Nugmanova, Raushan; Brady, Declan; Bottrill, Andrew R.; Vaughan, Sue; Brochet, Mathieu; Bollen, Mathieu; Pain, Arnab; Holder, Anthony A.; Guttery, David S.; Tewari, Rita

Abstract

PP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the malaria parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes. Using real-time live-cell and ultrastructural imaging, conditional gene knockdown, RNA-seq and proteomic approaches, we show that Plasmodium PP1 is implicated in both mitotic exit and, potentially, establishing cell polarity during zygote development in the mosquito midgut, suggesting that small molecule inhibitors of PP1 should be explored for blocking parasite transmission.

Citation

Zeeshan, M., Pandey, R., Subudhi, A. K., Ferguson, D. J., Kaur, G., Rashpa, R., …Tewari, R. (2021). Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages. Communications Biology, 4(1), Article 760. https://doi.org/10.1038/s42003-021-02273-0

• Journal Article Type: Article
• Acceptance Date: May 25, 2021
• Online Publication Date: Jun 18, 2021
• Publication Date: Jun 18, 2021
• Deposit Date: Jun 10, 2021
• Publicly Available Date: Jun 21, 2021
• Journal: Communications Biology
• Electronic ISSN: 2399-3642
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 4
• Issue: 1
• Article Number: 760
• DOI: https://doi.org/10.1038/s42003-021-02273-0
• Public URL: https://nottingham-repository.worktribe.com/output/5653856
• Publisher URL: https://www.nature.com/articles/s42003-021-02273-0
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