Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes

Roques, Magali and Wall, Richard J and Douglass, Alexander P and Ramaprasad, Abhinay and Ferguson, David J P and Kaindama, Mbinda L and Brusini, Lorenzo and Joshi, Nimitray and Rchiad, Zineb and Brady, Declan and Guttery, David S and Wheatley, Sally P and Yamano, Hiroyuki and Holder, Anthony A and Pain, Arnab and Wickstead, Bill and Tewari, Rita (2015) Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes. PloS Pathogens, 11 (11). e1005273/1-e1005273/29. ISSN 1553-7374

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Abstract

Cell-cycle progression and cell division in eukaryotes are governed in part by the cyclin family and their regulation of cyclin-dependent kinases (CDKs). Cyclins are very well characterised in model systems such as yeast and human cells, but surprisingly little is known about their number and role in Plasmodium, the unicellular protozoan parasite that causes malaria. Malaria parasite cell division and proliferation differs from that of many eukaryotes. During its life cycle it undergoes two types of mitosis: endomitosis in asexual stages and an extremely rapid mitotic process during male gametogenesis. Both schizogony (producing merozoites) in host liver and red blood cells, and sporogony (producing sporozoites) in the mosquito vector, are endomitotic with repeated nuclear replication, without chromosome condensation, before cell division. The role of specific cyclins during Plasmodium cell proliferation was unknown. We show here that the Plasmodium genome contains only three cyclin genes, representing an unusual repertoire of cyclin classes. Expression and reverse genetic analyses of the single Plant (P)-type cyclin, CYC3, in the rodent malaria parasite, Plasmodium berghei, revealed a cytoplasmic and nuclear location of the GFP-tagged protein throughout the lifecycle. Deletion of cyc3 resulted in defects in size, number and growth of oocysts, with abnormalities in budding and sporozoite formation. Furthermore, global transcript analysis of the cyc3-deleted and wild type parasites at gametocyte and ookinete stages identified differentially expressed genes required for signalling, invasion and oocyst development. Collectively these data suggest that cyc3 modulates oocyst endomitotic development in Plasmodium berghei.

Item Type: Article
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: https://doi.org/10.1371/journal.ppat.1005273
Depositing User: Wickstead, Bill
Date Deposited: 18 Jul 2016 09:44
Last Modified: 26 Sep 2016 14:46
URI: http://eprints.nottingham.ac.uk/id/eprint/35093

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