Limits...
Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.

Roques M, Wall RJ, Douglass AP, Ramaprasad A, Ferguson DJ, Kaindama ML, Brusini L, Joshi N, Rchiad Z, Brady D, Guttery DS, Wheatley SP, Yamano H, Holder AA, Pain A, Wickstead B, Tewari R - PLoS Pathog. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.

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.

Show MeSH

Related in: MedlinePlus

Characterisation of the cyclin repertoire of the Apicomplexa.(A) Maximum likelihood phylogeny based on an alignment of cyclins from Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium parvum and Homo sapiens. CYCP1 and CYCH1 from Arabidopsis thaliana have been included for clarity. Topology support from bootstrapping is shown at nodes. (B) Distribution of cyclin families across Apicomplexa. Presence (filled dot) or absence (empty circle) of specific families of cyclin in each predicted proteome is shown. Dot area is proportional to number of putative proteins. The Group I cyclins in Cryptosporidium cannot be placed reliably into any specific families within the group (“Orphaned”). *The Plasmodium berghei predicted proteome (release 9.3; plasmodb.org/) contains no apparent orthologue of CYC1, as the likely gene encoding the protein on Chromosome 13 (downstream of PBANKA_132730, syntenic with cyc1 in other Plasmodium species) is interrupted by a sequence gap.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4643991&req=5

ppat.1005273.g001: Characterisation of the cyclin repertoire of the Apicomplexa.(A) Maximum likelihood phylogeny based on an alignment of cyclins from Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium parvum and Homo sapiens. CYCP1 and CYCH1 from Arabidopsis thaliana have been included for clarity. Topology support from bootstrapping is shown at nodes. (B) Distribution of cyclin families across Apicomplexa. Presence (filled dot) or absence (empty circle) of specific families of cyclin in each predicted proteome is shown. Dot area is proportional to number of putative proteins. The Group I cyclins in Cryptosporidium cannot be placed reliably into any specific families within the group (“Orphaned”). *The Plasmodium berghei predicted proteome (release 9.3; plasmodb.org/) contains no apparent orthologue of CYC1, as the likely gene encoding the protein on Chromosome 13 (downstream of PBANKA_132730, syntenic with cyc1 in other Plasmodium species) is interrupted by a sequence gap.

Mentions: To investigate the Plasmodium cyclin repertoire, we built a pan-cyclin hidden Markov model (HMM) of cyclins from a range of model species and used this to identify putative cyclins in a wide range of eukaryotes (see Methods). Our HMM showed good sensitivity, identifying full cyclin repertoires in diverse organisms not included in the seed alignment, and the resultant proteins sequences were aligned, trimmed to conserved regions and classified by constructing phylogenetic trees (Fig 1A and S1 Fig).


Plasmodium P-Type Cyclin CYC3 Modulates Endomitotic Growth during Oocyst Development in Mosquitoes.

Roques M, Wall RJ, Douglass AP, Ramaprasad A, Ferguson DJ, Kaindama ML, Brusini L, Joshi N, Rchiad Z, Brady D, Guttery DS, Wheatley SP, Yamano H, Holder AA, Pain A, Wickstead B, Tewari R - PLoS Pathog. (2015)

Characterisation of the cyclin repertoire of the Apicomplexa.(A) Maximum likelihood phylogeny based on an alignment of cyclins from Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium parvum and Homo sapiens. CYCP1 and CYCH1 from Arabidopsis thaliana have been included for clarity. Topology support from bootstrapping is shown at nodes. (B) Distribution of cyclin families across Apicomplexa. Presence (filled dot) or absence (empty circle) of specific families of cyclin in each predicted proteome is shown. Dot area is proportional to number of putative proteins. The Group I cyclins in Cryptosporidium cannot be placed reliably into any specific families within the group (“Orphaned”). *The Plasmodium berghei predicted proteome (release 9.3; plasmodb.org/) contains no apparent orthologue of CYC1, as the likely gene encoding the protein on Chromosome 13 (downstream of PBANKA_132730, syntenic with cyc1 in other Plasmodium species) is interrupted by a sequence gap.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643991&req=5

ppat.1005273.g001: Characterisation of the cyclin repertoire of the Apicomplexa.(A) Maximum likelihood phylogeny based on an alignment of cyclins from Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium parvum and Homo sapiens. CYCP1 and CYCH1 from Arabidopsis thaliana have been included for clarity. Topology support from bootstrapping is shown at nodes. (B) Distribution of cyclin families across Apicomplexa. Presence (filled dot) or absence (empty circle) of specific families of cyclin in each predicted proteome is shown. Dot area is proportional to number of putative proteins. The Group I cyclins in Cryptosporidium cannot be placed reliably into any specific families within the group (“Orphaned”). *The Plasmodium berghei predicted proteome (release 9.3; plasmodb.org/) contains no apparent orthologue of CYC1, as the likely gene encoding the protein on Chromosome 13 (downstream of PBANKA_132730, syntenic with cyc1 in other Plasmodium species) is interrupted by a sequence gap.
Mentions: To investigate the Plasmodium cyclin repertoire, we built a pan-cyclin hidden Markov model (HMM) of cyclins from a range of model species and used this to identify putative cyclins in a wide range of eukaryotes (see Methods). Our HMM showed good sensitivity, identifying full cyclin repertoires in diverse organisms not included in the seed alignment, and the resultant proteins sequences were aligned, trimmed to conserved regions and classified by constructing phylogenetic trees (Fig 1A and S1 Fig).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom.

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.

Show MeSH
Related in: MedlinePlus