Commit and Transmit: Molecular Players in Plasmodium Sexual Development and Zygote Differentiation

Guttery, David S.; Roques, Magali; Holder, Anthony A.; Tewari, Rita

doi:10.1016/j.pt.2015.08.002

Cited by 60 publications

(56 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While a female gametocyte forms a single macrogamete, the male gamete undergoes three mitotic divisions, assembles eight intracytoplasmic axonemes, and produces eight flagellated microgametes in just 10–15 min (Guttery et al., 2015). “Exflagellation” occurs when male microgametes use microtubule-based movements to leave the erythrocyte host and bind egressed macrogametes, and exflagellation centers (ECs), made of gametes attached to erythrocytes, can be readily observed by microscopy.…”

Section: Resultsmentioning

confidence: 99%

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Bargieri

Thiberge

Tay

et al. 2016

Cell Host & Microbe

View full text Add to dashboard Cite

SummarySurface-associated TRAP (thrombospondin-related anonymous protein) family proteins are conserved across the phylum of apicomplexan parasites. TRAP proteins are thought to play an integral role in parasite motility and cell invasion by linking the extracellular environment with the parasite submembrane actomyosin motor. Blood stage forms of the malaria parasite Plasmodium express a TRAP family protein called merozoite-TRAP (MTRAP) that has been implicated in erythrocyte invasion. Using MTRAP-deficient mutants of the rodent-infecting P. berghei and human-infecting P. falciparum parasites, we show that MTRAP is dispensable for erythrocyte invasion. Instead, MTRAP is essential for gamete egress from erythrocytes, where it is necessary for the disruption of the gamete-containing parasitophorous vacuole membrane, and thus for parasite transmission to mosquitoes. This indicates that motor-binding TRAP family members function not just in parasite motility and cell invasion but also in membrane disruption and cell egress.

show abstract

Section: Resultsmentioning

confidence: 99%

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Bargieri

Thiberge

Tay

et al. 2016

Cell Host & Microbe

View full text Add to dashboard Cite

show abstract

“…Three rounds of rapid genome duplication (from haploid to octoploid) without concomitant nuclear division (endoreduplication) are followed by chromosome condensation and nuclear budding into the flagellated male gamete during exflagellation within 12 to 15 min after activation (Arnot and Gull, 1998;Janse et al, 1988;Sinden, 1983). The resultant eight flagellated microgametes, each contain a haploid genome (Guttery et al, 2015;Sinden et al, 2010). Fertilization of the female gamete results in a diploid zygote, which develops and differentiates over a 24-hour period into a motile ookinete in the mosquito gut ( Fig.…”

Section: Introductionmentioning

confidence: 99%

“…Reductive division to haploidy presumably occurs in the subsequent oocyst during sporozoite formation (Guttery et al, 2015;Sinden, 1991a;Sinden, 1991b). These different stages of cell division and proliferation indicate that the parasite has evolved alternate modes of chromosome replication, condensation and segregation, and nuclear and cell division at different stages in the life cycle.…”

Section: Introductionmentioning

confidence: 99%

Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation

Pandey

Zeeshan

Ferguson

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Eukaryotic cell proliferation requires chromosome replication and precise segregation, followed by cell division, to ensure daughter cells have identical genomic copies. The kinetochore is a multi-protein structure assembled on chromosome centromeres, which mediates attachment to spindle microtubules and chromosome segregation during mitosis. Plasmodium spp., the causative agent of malaria, undergoes closed mitosis with an intact nuclear membrane and intranuclear mitotic spindle. However, the regulation of the main events of mitosis and meiosis, including chromosome segregation, is poorly understood in this parasite. In part this is due to a distinct lack of markers for tracking kinetochore dynamics. Since NDC80 is the conserved component of the kinetochore complex, we labelled NDC80 with either a C-terminal GFP or mCherry tag by recombination at the endogenous locus to generate transgenic lines of the rodent malaria parasite Plasmodium berghei. We show that NDC80 is located at a single cluster of all kinetochores and examine its spatio-temporal dynamics throughout all proliferative stages of the parasite life cycle.We also compare the location of NDC80 with that of the kinetochore using electron microscopy. These transgenic parasite lines are a very useful resource to identify and study the kinetochore complex and follow chromosome dynamics during malaria parasite development.

show abstract

“…Haploid sexual progenitor cells, male and female gametocytes, remain arrested early in the cell cycle within red blood cells and produce gametes only following ingestion in a blood meal within a mosquito gut where environmental conditions, including temperature, pH and mosquito factors such as xanthurenic acid, are optimal for gametocyte activation [27,28]. Male gametocytes undergo three successive rounds of rapid DNA replication producing an 8N nucleus within 15 minutes of activation, followed by exflagellation to release eight flagellated male gametes [29,30]. Plasmodium lacks a classical centriole to nucleate spindle microtubules and drive spindle formation; however there is evidence from electron microscopy for the presence of a putative microtubule organizing centre (MTOC) embedded in the nuclear membrane, which initiates the polymerization of spindle microtubules [31,32].…”

Section: Introductionmentioning

confidence: 99%

Plasmodium Kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Zeeshan

Shilliday

Liu

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

Kinesin-8 proteins are microtubule motors that are often involved in regulation of mitotic spindle length and chromosome alignment. They move towards the ends of spindle microtubules and regulate the dynamics of these ends due, at least in some species, to their microtubule depolymerization activity. Plasmodium spp. exhibit an atypical endomitotic cell division in which chromosome condensation and spindle dynamics are not well understood in the different proliferative stages. Genome-wide homology analysis of Plasmodium spp. revealed the presence of two Kinesin-8 motor proteins (Kinesin-8X and Kinesin-8B). Here we have studied the biochemical properties of Kinesin-8X and its role in parasite proliferation. In vitro, Kinesin-8X showed motile and depolymerization activities like other Kinesin-8 motors. To understand its role in cell division, we have used protein tagging and live cell imaging to define the location of Plasmodium Kinesin-8X during all proliferative stages of the P berghei life cycle. Furthermore, we have used gene targeting to analyse the function of Kinesin-8X. The results reveal a spatio-temporal involvement of Kinesin-8X in spindle dynamics and its association with both mitotic and meiotic spindles and the putative microtubule organising centre (MTOC). Deletion of the Kinesin-8X gene showed that this protein is required for endomitotic division during oocyst development and is therefore necessary for parasite replication within the mosquito gut, and for transmission to the vertebrate host. Consistently, transcriptome analysis of Δkinesin-8X parasites reveals modulated expression of genes involved mainly in microtubulebased processes, chromosome organisation and the regulation of gene expression supporting a role in cell division. 4 Author SummaryKinesins are microtubule-based motors that play key roles in intracellular transport, cell division and motility. Members of the Kinesin-8 family contribute to chromosome alignment during cell division in many eukaryotes. However, the roles of kinesins in the atypical cell division in Plasmodium, the causative agent of malaria, is not known.In contrast to many other eukaryotes, Plasmodium proliferates by endomitosis, in which genome replication and division occur within a nucleus bounded by a persistent nuclear envelope. We show that the Plasmodium genome encodes only nine kinesins and we further investigate the role of Kinesin-8X throughout the Plasmodium life cycle using biochemical and gene targeting approaches. We show that Plasmodium Kinesin-8X has microtubule-based motility and depolymerization activity. We also show that Kinesin-8X is probably localized on putative MTOCs and spindles during cell division in most of the stages of P. berghei life cycle. By gene deletion we demonstrate that Kinesin-8X is essential for normal oocyst development and sporozoite formation. Genome-wide RNA analysis of Δkinesin-8X parasites reveals modulated expression of genes involved in microtubule-based processes. Overall, the data suggest that Kinesin-8X is a molecular ...

show abstract

Commit and Transmit: Molecular Players in Plasmodium Sexual Development and Zygote Differentiation

Cited by 60 publications

References 86 publications

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Plasmodium Merozoite TRAP Family Protein Is Essential for Vacuole Membrane Disruption and Gamete Egress from Erythrocytes

Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation

Plasmodium Kinesin-8X associates with mitotic spindles and is essential for oocyst development during parasite proliferation and transmission

Contact Info

Product

Resources

About