Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes
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 i...
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Public Library of Science
2015
|
| Online Access: | https://eprints.nottingham.ac.uk/35093/ |
| _version_ | 1848795001027297280 |
|---|---|
| author | Roques, Magali Wall, Richard J Douglass, Alexander P Ramaprasad, Abhinay Ferguson, David J P Kaindama, Mbinda L Brusini, Lorenzo Joshi, Nimitray Rchiad, Zineb Brady, Declan Guttery, David S Wheatley, Sally P Yamano, Hiroyuki Holder, Anthony A Pain, Arnab Wickstead, Bill Tewari, Rita |
| author_facet | Roques, Magali Wall, Richard J Douglass, Alexander P Ramaprasad, Abhinay Ferguson, David J P Kaindama, Mbinda L Brusini, Lorenzo Joshi, Nimitray Rchiad, Zineb Brady, Declan Guttery, David S Wheatley, Sally P Yamano, Hiroyuki Holder, Anthony A Pain, Arnab Wickstead, Bill Tewari, Rita |
| author_sort | Roques, Magali |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:25:08Z |
| format | Article |
| id | nottingham-35093 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:25:08Z |
| publishDate | 2015 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-350932020-05-04T17:23:30Z https://eprints.nottingham.ac.uk/35093/ Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes Roques, Magali Wall, Richard J Douglass, Alexander P Ramaprasad, Abhinay Ferguson, David J P Kaindama, Mbinda L Brusini, Lorenzo Joshi, Nimitray Rchiad, Zineb Brady, Declan Guttery, David S Wheatley, Sally P Yamano, Hiroyuki Holder, Anthony A Pain, Arnab Wickstead, Bill Tewari, Rita 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. Public Library of Science 2015-11-13 Article PeerReviewed Roques, Magali, Wall, Richard J, Douglass, Alexander P, Ramaprasad, Abhinay, Ferguson, David J P, Kaindama, Mbinda L, Brusini, Lorenzo, Joshi, Nimitray, Rchiad, Zineb, Brady, Declan, Guttery, David S, Wheatley, Sally P, Yamano, Hiroyuki, Holder, Anthony A, Pain, Arnab, 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 http://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1005273 doi:10.1371/journal.ppat.1005273 doi:10.1371/journal.ppat.1005273 |
| spellingShingle | Roques, Magali Wall, Richard J Douglass, Alexander P Ramaprasad, Abhinay Ferguson, David J P Kaindama, Mbinda L Brusini, Lorenzo Joshi, Nimitray Rchiad, Zineb Brady, Declan Guttery, David S Wheatley, Sally P Yamano, Hiroyuki Holder, Anthony A Pain, Arnab Wickstead, Bill Tewari, Rita Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes |
| title | Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes |
| title_full | Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes |
| title_fullStr | Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes |
| title_full_unstemmed | Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes |
| title_short | Plasmodium P-type cyclin CYC3 modulates endomitotic growth during oocyst development in mosquitoes |
| title_sort | plasmodium p-type cyclin cyc3 modulates endomitotic growth during oocyst development in mosquitoes |
| url | https://eprints.nottingham.ac.uk/35093/ https://eprints.nottingham.ac.uk/35093/ https://eprints.nottingham.ac.uk/35093/ |