A Plasmodium falciparum Cysteine Rich Secretory protein uniquely localizes to one end of male gametes

2022 ◽  
pp. 111447
Author(s):  
Sudhir Kumar ◽  
Amanda S. Leeb ◽  
Ashley M. Vaughan ◽  
Stefan H.I. Kappe
Keyword(s):  
Plasmodium Falciparum ◽  
Secretory Protein ◽  
Male Gametes

scholarly journals Role of a patatin-like phospholipase in Plasmodium falciparum gametogenesis and malaria transmission

2019 ◽  
Vol 116 (35) ◽  
pp. 17498-17508 ◽  
Author(s):  
Pallavi Singh ◽  
Aditi Alaganan ◽  
Kunal R. More ◽  
Audrey Lorthiois ◽  
Sabine Thiberge ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Membrane Remodeling ◽  
Gene Encoding ◽  
Conditional Deletion ◽  
Male Gametes ◽  
Complex Process ◽  
Intracellular Vesicles ◽  
Vesicle Secretion

Transmission of Plasmodium falciparum involves a complex process that starts with the ingestion of gametocytes by female Anopheles mosquitoes during a blood meal. Activation of gametocytes in the mosquito midgut triggers “rounding up” followed by egress of both male and female gametes. Egress requires secretion of a perforin-like protein, PfPLP2, from intracellular vesicles to the periphery, which leads to destabilization of peripheral membranes. Male gametes also develop flagella, which assist in binding female gametes for fertilization. This process of gametogenesis, which is key to malaria transmission, involves extensive membrane remodeling as well as vesicular discharge. Phospholipase A2 enzymes (PLA2) are known to mediate membrane remodeling and vesicle secretion in diverse organisms. Here, we show that a P. falciparum patatin-like phospholipase (PfPATPL1) with PLA2 activity plays a key role in gametogenesis. Conditional deletion of the gene encoding PfPATPL1 does not affect P. falciparum blood stage growth or gametocyte development but reduces efficiency of rounding up, egress, and exflagellation of gametocytes following activation. Interestingly, deletion of the PfPATPL1 gene inhibits secretion of PfPLP2, reducing the efficiency of gamete egress. Deletion of PfPATPL1 also reduces the efficiency of oocyst formation in mosquitoes. These studies demonstrate that PfPATPL1 plays a role in gametogenesis, thereby identifying PLA2 phospholipases such as PfPATPL1 as potential targets for the development of drugs to block malaria transmission.

Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum

1993 ◽  
Vol 13 (12) ◽  
pp. 7349-7357
Author(s):  
A B Vaidya ◽  
J Morrisey ◽  
C V Plowe ◽  
D C Kaslow ◽  
T E Wellems
Keyword(s):  
Plasmodium Falciparum ◽  
Single Strand Conformation Polymorphism ◽  
Cytoplasmic Inheritance ◽  
Polymorphism Analysis ◽  
Inheritance Pattern ◽  
Dna Molecules ◽  
Genetic Crosses ◽  
Male Gametes ◽  
Cytoplasmic Dna ◽  
Geographical Regions

Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions.

scholarly journals Apicoplast and Mitochondrion in Gametocytogenesis of Plasmodium falciparum

2008 ◽  
Vol 8 (1) ◽  
pp. 128-132 ◽  
Author(s):  
Noriko Okamoto ◽  
Timothy P. Spurck ◽  
Christopher D. Goodman ◽  
Geoffrey I. McFadden
Keyword(s):  
Plasmodium Falciparum ◽  
Live Cell Imaging ◽  
Cell Imaging ◽  
Maternal Inheritance ◽  
Live Cell ◽  
Close Connection ◽  
Morphological Development ◽  
Malaria Parasites ◽  
Human Malaria ◽  
Male Gametes

ABSTRACT Live cell imaging of human malaria parasites Plasmodium falciparum during gametocytogenesis revealed that the apicoplast does not grow, whereas the mitochondrion undergoes remarkable morphological development. A close connection of the two organelles is consistently maintained. The apicoplast and mitochondrion are not components of the male gametes, suggesting maternal inheritance.

scholarly journals Male and Female Plasmodium falciparum Mature Gametocytes Show Different Responses to Antimalarial Drugs

2013 ◽  
Vol 57 (7) ◽  
pp. 3268-3274 ◽  
Author(s):  
Michael J. Delves ◽  
Andrea Ruecker ◽  
Ursula Straschil ◽  
Jöel Lelièvre ◽  
Sara Marques ◽  
...  
Keyword(s):  
Methylene Blue ◽  
Plasmodium Falciparum ◽  
Mature Male ◽  
Mammalian Host ◽  
Parasite Transmission ◽  
Significant Activity ◽  
Male And Female ◽  
Transmission Blocking ◽  
Content Type ◽  
Male Gametes

ABSTRACTIt is the mature gametocytes ofPlasmodiumthat are solely responsible for parasite transmission from the mammalian host to the mosquito. They are therefore a logical target for transmission-blocking antimalarial interventions, which aim to break the cycle of reinfection and reduce the prevalence of malaria cases. Gametocytes, however, are not a homogeneous cell population. They are sexually dimorphic, and both males and females are required for parasite transmission. Using two bioassays, we explored the effects of 20 antimalarials on the functional viability of both male and female mature gametocytes ofPlasmodium falciparum. We show that mature male gametocytes (as reported by their ability to produce male gametes, i.e., to exflagellate) are sensitive to antifolates, some endoperoxides, methylene blue, and thiostrepton, with submicromolar 50% inhibitory concentrations (IC50s), whereas female gametocytes (as reported by their ability to activate and form gametes expressing the marker Pfs25) are much less sensitive to antimalarial intervention, with only methylene blue and thiostrepton showing any significant activity. These findings show firstly that the antimalarial responses of male and female gametocytes differ and secondly that the mature male gametocyte should be considered a more vulnerable target than the female gametocyte for transmission-blocking drugs. Given the female-biased sex ratio ofPlasmodium falciparum(∼3 to 5 females:1 male), current gametocyte assays without a sex-specific readout are unlikely to identify male-targeted compounds and prioritize them for further development. Both assays reported here are being scaled up to at least medium throughput and will permit identification of key transmission-blocking molecules that have been overlooked by other screening campaigns.

scholarly journals Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum.

1993 ◽  
Vol 13 (12) ◽  
pp. 7349-7357 ◽  
Author(s):  
A B Vaidya ◽  
J Morrisey ◽  
C V Plowe ◽  
D C Kaslow ◽  
T E Wellems
Keyword(s):  
Plasmodium Falciparum ◽  
Single Strand Conformation Polymorphism ◽  
Cytoplasmic Inheritance ◽  
Polymorphism Analysis ◽  
Inheritance Pattern ◽  
Dna Molecules ◽  
Genetic Crosses ◽  
Male Gametes ◽  
Cytoplasmic Dna ◽  
Geographical Regions

Malarial parasites have two highly conserved cytoplasmic DNA molecules: a 6-kb tandemly arrayed DNA that has characteristics of a mitochondrial genome, and a 35-kb circular DNA that encodes functions commonly found in chloroplasts. We examined the inheritance pattern of these elements in two genetic crosses of Plasmodium falciparum clones. Parent-specific oligonucleotide probes and single-strand conformation polymorphism analysis identified single nucleotide changes that distinguished the parental 6- and 35-kb DNA molecules in the progeny. In all 16 independent recombinant progeny of a cross between a Central American clone, HB3, and a Southeast Asian clone, Dd2, the 6- and 35-kb DNAs were inherited from the Dd2 parent. In all nine independent recombinant progeny of a cross between clone HB3 and a likely African clone, 3D7, the 6-kb DNA was inherited from the 3D7 parent. Inheritance of cytoplasmic genomes of the Dd2 and 3D7 parents was, therefore, dominant over that of the HB3 parent. Cytoplasmic DNA molecules were found almost exclusively in the female gametes of malarial parasites; hence, clone HB3 did not appear to have served as a maternal parent for the progeny of two crosses. Defective differentiation into male gametes by clone Dd2 is likely to be a reason for the cytoplasmic inheritance pattern seen in the HB3 x Dd2 cross. However, incompetence of male or female gametes is unlikely to explain the uniparental dominance in recombinant progeny of the HB3 x 3D7 cross, since both parents readily self-fertilized and completed the malaria life cycle on their own. Instead, the data suggest unidirectional parental incompatibility in cross-fertilization of these malarial parasites, where a usually cosexual parental clone can participate only as a male or as a female. Such an incompatibility may be speculated as indicating an early phase of reproductive isolation of P. falciparum clones from different geographical regions.

scholarly journals mRNA localization mediates maturation of cytoplasmic cilia in Drosophila spermatogenesis

2020 ◽  
Vol 219 (9) ◽  
Author(s):  
Jaclyn M. Fingerhut ◽  
Yukiko M. Yamashita
Keyword(s):  
Plasmodium Falciparum ◽  
Drosophila Melanogaster ◽  
Motor Proteins ◽  
Mrna Localization ◽  
Precise Localization ◽  
Granule Formation ◽  
Male Gametes ◽  
Dynein Motor ◽  
Axonemal Dynein

Cytoplasmic cilia, a specialized type of cilia in which the axoneme resides within the cytoplasm rather than within the ciliary compartment, are proposed to allow for the efficient assembly of very long cilia. Despite being found diversely in male gametes (e.g., Plasmodium falciparum microgametocytes and human and Drosophila melanogaster sperm), very little is known about cytoplasmic cilia assembly. Here, we show that a novel RNP granule containing the mRNAs for axonemal dynein motor proteins becomes highly polarized to the distal end of the cilia during cytoplasmic ciliogenesis in Drosophila sperm. This allows for the incorporation of these axonemal dyneins into the axoneme directly from the cytoplasm, possibly by localizing translation. We found that this RNP granule contains the proteins Reptin and Pontin, loss of which perturbs granule formation and prevents incorporation of the axonemal dyneins, leading to sterility. We propose that cytoplasmic cilia assembly requires the precise localization of mRNAs encoding key axonemal constituents, allowing these proteins to incorporate efficiently into the axoneme.

Ultrastructural observations on the in vitro cytoadherence of Plasmodium falciparum infected red blood cells

1990 ◽  
Vol 48 (3) ◽  
pp. 914-915
Author(s):  
D.J.P. Ferguson ◽  
A.R. Berendt ◽  
J. Tansey ◽  
K. Marsh ◽  
C.I. Newbold
Keyword(s):  
Plasmodium Falciparum ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Umbilical Vein ◽  
Cell Types ◽  
Amelanotic Melanoma ◽  
Cytoplasmic Process ◽  
Umbilical Vein Endothelial Cells

In human malaria, the most serious clinical manifestation is cerebral malaria (CM) due to infection with Plasmodium falciparum. The pathology of CM is thought to relate to the fact that red blood cells containing mature forms of the parasite (PRBC) cytoadhere or sequester to post capillary venules of various tissues including the brain. This in vivo phenomenon has been studied in vitro by examining the cytoadherence of PRBCs to various cell types and purified proteins. To date, three Ijiost receptor molecules have been identified; CD36, ICAM-1 and thrombospondin. The specific changes in the PRBC membrane which mediate cytoadherence are less well understood, but they include the sub-membranous deposition of electron-dense material resulting in surface deformations called knobs. Knobs were thought to be essential for cytoadherence, lput recent work has shown that certain knob-negative (K-) lines can cytoadhere. In the present study, we have used electron microscopy to re-examine the interactions between K+ PRBCs and both C32 amelanotic melanoma cells and human umbilical vein endothelial cells (HUVEC).We confirm previous data demonstrating that C32 cells possess numerous microvilli which adhere to the PRBC, mainly via the knobs (Fig. 1). In contrast, the HUVEC were relatively smooth and the PRBCs appeared partially flattened onto the cell surface (Fig. 2). Furthermore, many of the PRBCs exhibited an invagination of the limiting membrane in the attachment zone, often containing a cytoplasmic process from the endothelial cell (Fig. 2).

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