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

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

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

AbstractPP1 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.
Original languageEnglish (US)
JournalCommunications Biology
Volume4
Issue number1
DOIs
StatePublished - Jun 18 2021

Bibliographical note

KAUST Repository Item: Exported on 2021-06-21
Acknowledged KAUST grant number(s): BAS/1/1020-01-01, CRG, OSR-2018-CRG6-3392
Acknowledgements: We thank Julie Rodgers for helping to maintain the insectary and other technical works, and the personnel at the Bioscience Core Laboratory (BCL) in KAUST for sequencing the RNA samples and producing the raw datasets. This work was supported by: MRC UK (G0900278, MR/K011782/1, MR/N023048/1) and BBSRC (BB/N017609/1) to R.T. and M.Z.; the Francis Crick Institute (FC001097), the Cancer Research UK (FC001097), the UK Medical Research Council (FC001097), and the Wellcome Trust (FC001097) to A.A.H.; the Swiss National Science Foundation project grant 31003A_179321 to M.Br; a faculty baseline fund (BAS/1/1020-01-01) and a Competitive Research Grant (CRG) award from OSR (OSR-2018-CRG6-3392) from the King Abdullah University of Science and Technology to A.P.; M.Br is an INSERM and EMBO young investigator. This research was funded in whole, or in part, by the Wellcome Trust [FC001097]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

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