Plasmodium berghei α-tubulin II: A role in both male gamete formation and asexual blood stages

Kooij, Taco W. A.; Franke-Fayard, Blandine; Renz, Jasper; Kroeze, Hans; Dooren, Maaike W. van; Ramesar, Jai; Augustijn, Kevin D.; Janse, Chris J.; Waters, Andrew P.

doi:10.1016/j.molbiopara.2005.07.003

Cited by 29 publications

(31 citation statements)

References 36 publications

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“…10, 2011 MINIREVIEWS 479 Tubulin proteins, the building blocks of microtubules, are highly conserved among eukaryotes, and there are several antibodies and other reagents for tubulins that have been used to stain P. falciparum microtubules for fluorescence microscopy (24,42,53,74). Studies using fluorescent probes against tubulins have highlighted the variety of P. falciparum microtubule structures (53) that are comprised of differentially expressed tubulin isotypes and posttranslational modifications (24,38,53). In addition, tubulin fluorescence has been used to correlate spindle development with the nuclear cycle (7,42,53) and to characterize the disruption of mitotic structures in response to antimalarial drug treatments (25,74).…”

Section: Figmentioning

confidence: 99%

Mitosis in the Human Malaria Parasite Plasmodium falciparum

2011

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Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. SERIAL MITOSIS IS A COMMON THEME IN MALARIA PARASITE REPRODUCTIONThere are four critical points in the life cycle of Plasmodium parasites in which a small number of parasites rapidly multiply to generate much larger populations (60). These life cycle stages are male gamete development (72), sporozoite formation (5, 13), liver-stage development (68), and blood-stage asexual reproduction (9, 60). The first two of these processes occur within the mosquito vector, and the second two processes take place in the vertebrate host. During each of these Plasmodium life cycle stages, the parasites increase their numbers by using serial rounds of mitosis to create multinuclear cells and then orchestrating mass cytokinesis events to release their progeny (71). Mitosis is the process by which eukaryotic cells segregate their chromosomes in preparation for cell division (33,47,51).To create male gametes in preparation for sexual reproduction, the parasite begins with a haploid (1n) cell called a microgametocyte which is ingested by the mosquito during a blood meal (34,72). Within 12 min, this microgametocyte undergoes three rapid rounds of DNA synthesis and mitosis to generate a cell with an 8n genomic complement (35,36,73). Over the next 3 min, these genomes separate from one another and eight new haploid (1n) male gametes begin to assemble from the surface of the original cell (4, 69, 71).Within the mosquito midgut, a small number of the male gametes will fuse with female gametes that have also developed in this compartment, and this fusion will create diploid (2n) zygotes (15). These zygotes develop into motile ookinetes (4n) (36) that ultimately become embedded in the basal lamina beneath the midgut epithelial wall as oocysts (14). Over the course of several days, a single oocyst undergoes 10 to 11 rounds of DNA synthesis and mitosis to create a syncytial cell (sporoblast) with thousands of nuclei (61,70,82). In a massive cytokinesis event, thousands of haploid (1n) daughter sporozoites assemble from the surface of the mother cell (61, 67), and these infective sporozo...

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Section: Figmentioning

confidence: 99%

Mitosis in the Human Malaria Parasite Plasmodium falciparum

2011

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“…The construct pL1156 is integrated by double crossover recombination and does not contain a drug-selectable marker gene. The DNA construct for the generation of this reporter line (Supplemental Figure S2A, see http://ajp.amjpathol.org) was made by replacing the ␣-tubulin II promoter of pL0024 14 with the ama1 promoter (EcoRV/BamHI fragment of pL0010). The ama1-gfpm3 (EcoRV/KpnI) fragment of this plasmid was subcloned in plasmid BSSK to create plasmid BSSKama1-gfp-3Јutr.…”

Section: Generation Of Parasites Lines Expressing Luciferasementioning

confidence: 99%

“…18 Flow cytometry analysis of cell cycle progression, following in vitro synchronized Hoechst 33258-stained blood-stage parasites, 18 revealed that ⌬pm4 parasites have a prolonged cell cycle as shown by the delay in the onset of schizogony (length of the G 1 phase) by approximately 3 hours and a similar delay in the production of mature schizonts (end of the S/M phase) ( Table 1 and Supplemental Figure S4, see http://ajp.amjpathol.org). However, mature ⌬pm4 schizonts had normal numbers of daughter merozoites [12][13][14][15][16][17][18][19][20] (Table 1; Supplemental Figure S3, see http://ajp.amjpathol.org). Interestingly, in synchronous cultures the development of ⌬pm4 schizonts seemed to be less "synchronous" than in the wild-type cultures.…”

Section: Modest Growth Delay Of Blood Stages Of ⌬Pm4 Parasitesmentioning

confidence: 99%

Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental Malaria

Spaccapelo

Janse

Caterbi

et al. 2010

The American Journal of Pathology

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102

136

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Plasmodium parasites lacking plasmepsin 4 (PM4), an aspartic protease that functions in the lysosomal compartment and contributes to hemoglobin digestion , have only a modest decrease in the asexual blood-stage growth rate; however , PM4 deficiency in the rodent malaria parasite Plasmodium berghei results in significantly less virulence than that for the parental parasite. P. berghei ⌬pm4 parasites failed to induce experimental cerebral malaria (ECM) in ECMsusceptible mice , and ECM-resistant mice were able to clear infections.

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“…In P. falciparum , α-tubulin II is expressed in the sexual stages of the parasite, specifically in the male gametes (Rawlings et al, 1992), and it is located in the microgamete axoneme, a structure important for the motility of the parasite. In contrast, α-tubulin II is expressed in P. berghei in male gametocytes and also in the asexual stages (Kooij et al, 2005). Furthermore, a Tyr-phosphorylated site (Y363) was identified in both actin-1 and actin-2, as in silico prediction.…”

Section: Discussionmentioning

confidence: 98%

Protein phosphorylation during Plasmodium berghei gametogenesis

Alonso-Morales¹,

González-López²,

Cázares-Raga³

et al. 2015

Experimental Parasitology

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Plasmodium gametogenesis within the mosquito midgut is a complex differentiation process involving signaling mediated by phosphorylation, which modulate metabolic routes and protein synthesis required to complete this development. However, the mechanisms leading to gametogenesis activation are poorly understood. We analyzed protein phosphorylation during Plasmodium berghei gametogenesis in vitro in serum-free medium using bidimensional electrophoresis (2-DE) combined with immunoblotting (IB) and antibodies specific to phosphorylated serine, threonine and tyrosine. Approximately 75 protein exhibited phosphorylation changes, of which 23 were identified by mass spectrometry. These included components of the cytoskeleton, heat shock proteins, and proteins involved in DNA synthesis and signaling pathways among others. Novel phosphorylation events support a role for these proteins during gametogenesis. The phosphorylation sites of six of the identified proteins, HSP70, WD40 repeat protein msi1, enolase, actin-1 and two isoforms of large subunit of ribonucleoside reductase were investigated using TiO2 phosphopeptides enrichment and tandem mass spectrometry. In addition, transient exposure to hydroxyurea, an inhibitor of ribonucleoside reductase, impaired male gametocytes exflagellation in a dose-dependent manner, and provides a resource for functional studies.

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Plasmodium berghei α-tubulin II: A role in both male gamete formation and asexual blood stages

Cited by 29 publications

References 36 publications

Mitosis in the Human Malaria Parasite Plasmodium falciparum

Mitosis in the Human Malaria Parasite Plasmodium falciparum

Plasmepsin 4-Deficient Plasmodium berghei Are Virulence Attenuated and Induce Protective Immunity against Experimental Malaria

Protein phosphorylation during Plasmodium berghei gametogenesis

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