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Female inheritance of malarial lap genes is essential for mosquito transmission.

Raine JD, Ecker A, Mendoza J, Tewari R, Stanway RR, Sinden RE - PLoS Pathog. (2007)

Bottom Line: Sporozoite formation was rescued by a genetic cross with wild-type parasites, which results in the production of heterokaryotic polyploid ookinetes and oocysts, and ultimately infective Deltapblap sporozoites, but not if the individual Deltapblap parasite lines were crossed amongst each other.We conclude that the functions of PbLAPs1, 2, 4, and 6 are critical prior to the expression of the male-derived gene after microgametogenesis, fertilization, and meiosis, possibly in the gametocyte-to-ookinete period of differentiation.This phenotype is not seen in the other dividing forms of the mutant parasite lines in the liver and blood stages.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, United Kingdom.

ABSTRACT
Members of the LCCL/lectin adhesive-like protein (LAP) family, a family of six putative secreted proteins with predicted adhesive extracellular domains, have all been detected in the sexual and sporogonic stages of Plasmodium and have previously been predicted to play a role in parasite-mosquito interactions and/or immunomodulation. In this study we have investigated the function of PbLAP1, 2, 4, and 6. Through phenotypic analysis of Plasmodium berghei loss-of-function mutants, we have demonstrated that PbLAP2, 4, and 6, as previously shown for PbLAP1, are critical for oocyst maturation and sporozoite formation, and essential for transmission from mosquitoes to mice. Sporozoite formation was rescued by a genetic cross with wild-type parasites, which results in the production of heterokaryotic polyploid ookinetes and oocysts, and ultimately infective Deltapblap sporozoites, but not if the individual Deltapblap parasite lines were crossed amongst each other. Genetic crosses with female-deficient (Deltapbs47) and male-deficient (Deltapbs48/45) parasites show that the lethal phenotype is only rescued when the wild-type pblap gene is inherited from a female gametocyte, thus explaining the failure to rescue in the crosses between different Deltapblap parasite lines. We conclude that the functions of PbLAPs1, 2, 4, and 6 are critical prior to the expression of the male-derived gene after microgametogenesis, fertilization, and meiosis, possibly in the gametocyte-to-ookinete period of differentiation. The phenotypes detectable by cytological methods in the oocyst some 10 d after the critical period of activity suggests key roles of the LAPs or LAP-dependent processes in the regulation of the cell cycle, possibly in the regulation of cytoplasm-to-nuclear ratio, and, importantly, in the events of cytokinesis at sporozoite formation. This phenotype is not seen in the other dividing forms of the mutant parasite lines in the liver and blood stages.

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Oocyst and Sporozoite Development of wt and Δpblap ParasitesGraphical summary of oocyst numbers (A), midgut sporozoite numbers (B), and salivary gland sporozoite numbers (C) of wt and Δpblap parasites. Values of Δpblap parasites are given as mean % of wt (± standard error of the mean). Δlap1 as published in [2]. Please refer to Tables S3 and S4 for individual data.
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ppat-0030030-g001: Oocyst and Sporozoite Development of wt and Δpblap ParasitesGraphical summary of oocyst numbers (A), midgut sporozoite numbers (B), and salivary gland sporozoite numbers (C) of wt and Δpblap parasites. Values of Δpblap parasites are given as mean % of wt (± standard error of the mean). Δlap1 as published in [2]. Please refer to Tables S3 and S4 for individual data.

Mentions: All Δpblap parasites were capable of infecting Anopheles stephensi mosquitoes, and on day 10/11 post-infection (p.i.), numbers of oocysts were never less than those observed in wt-infected mosquitoes (Figure 1; Table S3). The diameters of Δpblap1, Δpblap2, and Δpblap6 oocysts were significantly larger than that of wt on day 7, and all mutants were larger on days 14 and 21 of infection (Figure S2).


Female inheritance of malarial lap genes is essential for mosquito transmission.

Raine JD, Ecker A, Mendoza J, Tewari R, Stanway RR, Sinden RE - PLoS Pathog. (2007)

Oocyst and Sporozoite Development of wt and Δpblap ParasitesGraphical summary of oocyst numbers (A), midgut sporozoite numbers (B), and salivary gland sporozoite numbers (C) of wt and Δpblap parasites. Values of Δpblap parasites are given as mean % of wt (± standard error of the mean). Δlap1 as published in [2]. Please refer to Tables S3 and S4 for individual data.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1808070&req=5

ppat-0030030-g001: Oocyst and Sporozoite Development of wt and Δpblap ParasitesGraphical summary of oocyst numbers (A), midgut sporozoite numbers (B), and salivary gland sporozoite numbers (C) of wt and Δpblap parasites. Values of Δpblap parasites are given as mean % of wt (± standard error of the mean). Δlap1 as published in [2]. Please refer to Tables S3 and S4 for individual data.
Mentions: All Δpblap parasites were capable of infecting Anopheles stephensi mosquitoes, and on day 10/11 post-infection (p.i.), numbers of oocysts were never less than those observed in wt-infected mosquitoes (Figure 1; Table S3). The diameters of Δpblap1, Δpblap2, and Δpblap6 oocysts were significantly larger than that of wt on day 7, and all mutants were larger on days 14 and 21 of infection (Figure S2).

Bottom Line: Sporozoite formation was rescued by a genetic cross with wild-type parasites, which results in the production of heterokaryotic polyploid ookinetes and oocysts, and ultimately infective Deltapblap sporozoites, but not if the individual Deltapblap parasite lines were crossed amongst each other.We conclude that the functions of PbLAPs1, 2, 4, and 6 are critical prior to the expression of the male-derived gene after microgametogenesis, fertilization, and meiosis, possibly in the gametocyte-to-ookinete period of differentiation.This phenotype is not seen in the other dividing forms of the mutant parasite lines in the liver and blood stages.

View Article: PubMed Central - PubMed

Affiliation: Division of Cell and Molecular Biology, Faculty of Natural Sciences, Imperial College London, London, United Kingdom.

ABSTRACT
Members of the LCCL/lectin adhesive-like protein (LAP) family, a family of six putative secreted proteins with predicted adhesive extracellular domains, have all been detected in the sexual and sporogonic stages of Plasmodium and have previously been predicted to play a role in parasite-mosquito interactions and/or immunomodulation. In this study we have investigated the function of PbLAP1, 2, 4, and 6. Through phenotypic analysis of Plasmodium berghei loss-of-function mutants, we have demonstrated that PbLAP2, 4, and 6, as previously shown for PbLAP1, are critical for oocyst maturation and sporozoite formation, and essential for transmission from mosquitoes to mice. Sporozoite formation was rescued by a genetic cross with wild-type parasites, which results in the production of heterokaryotic polyploid ookinetes and oocysts, and ultimately infective Deltapblap sporozoites, but not if the individual Deltapblap parasite lines were crossed amongst each other. Genetic crosses with female-deficient (Deltapbs47) and male-deficient (Deltapbs48/45) parasites show that the lethal phenotype is only rescued when the wild-type pblap gene is inherited from a female gametocyte, thus explaining the failure to rescue in the crosses between different Deltapblap parasite lines. We conclude that the functions of PbLAPs1, 2, 4, and 6 are critical prior to the expression of the male-derived gene after microgametogenesis, fertilization, and meiosis, possibly in the gametocyte-to-ookinete period of differentiation. The phenotypes detectable by cytological methods in the oocyst some 10 d after the critical period of activity suggests key roles of the LAPs or LAP-dependent processes in the regulation of the cell cycle, possibly in the regulation of cytoplasm-to-nuclear ratio, and, importantly, in the events of cytokinesis at sporozoite formation. This phenotype is not seen in the other dividing forms of the mutant parasite lines in the liver and blood stages.

Show MeSH
Related in: MedlinePlus