Journal Article


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

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 livecell 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.

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Authors

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

Oxford Brookes departments

Department of Biological and Medical Sciences

Dates

Year of publication: 2021
Date of RADAR deposit: 2022-06-15


Creative Commons License This work is licensed under a Creative Commons Attribution 4.0 International License


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