An axonemal intron splicing program sustains Plasmodium male development
Ontology highlight
ABSTRACT:
ORGANISM(S): Plasmodium Yoelii Yoelii 17xnl
SUBMITTER: 
Jing Yuan
PROVIDER: PXD044094 | iProX | Wed Jul 26 00:00:00 BST 2023
REPOSITORIES: iProX
Similar Datasets
Project description:The malaria-causing parasite Plasmodium has a complex life cycle involving both vertebrate and mosquito hosts. Sexual stages or gametocytes are the only stage competent for mosquito transmission. Gametogenesis of the male gametocyte requires rapid rounds of genome replication to form flagellated gametes. Here, we describe the discovery of a non-canonical Plasmodium actin-related protein 2/3 (Arp2/3) complex essential for DNA segregation during male gametogenesis. Plasmodium Arp2/3 dynamically localizes within the nucleus to the endomitotic spindle and interacts with a kinetochore protein. Deletion of key Arp2/3 subunits or interfering with actin polymerisation leads to the formation of sub-haploid male gametes and a complete block in transmission through delayed developmental arrest at the oocyst stage. Our work identified an evolutionary divergent protein complex in malaria parasites that offers potential targets for transmission-blocking interventions.
2025-04-22 | PXD046181 | Pride
Project description:The malaria-causing parasite Plasmodium has a complex life cycle involving both vertebrate and mosquito hosts. Sexual stages or gametocytes are the only stage competent for mosquito transmission. Gametogenesis of the male gametocyte requires rapid rounds of genome replication to form flagellated gametes. Here, we describe the discovery of a non-canonical Plasmodium actin-related protein 2/3 (Arp2/3) complex essential for DNA segregation during male gametogenesis. Plasmodium Arp2/3 dynamically localizes within the nucleus to the endomitotic spindle and interacts with a kinetochore protein. Deletion of key Arp2/3 subunits or interfering with actin polymerisation leads to the formation of sub-haploid male gametes and a complete block in transmission through delayed developmental arrest at the oocyst stage. Our work identified an evolutionary divergent protein complex in malaria parasites that offers potential targets for transmission-blocking interventions.
2025-04-22 | PXD051260 | Pride
Project description:The sexual stages are vital phases in malaria parasite transmission and are the targets of various interventions such as transmission blocking vaccines. The molecular mechanisms underlying sexual development, however, remain poorly understood. We report mappping of a determinant previously linked to a male gametocyte development defect in the P. falciparum Dd2 parasite to an 82 kb region on chromosome 12. In order to find a critical gene in this region, we compared gene expression pattern in sexual stage of the parasite between Dd2 and its normal gametocyte-producing ancestor W2 clones. The region contains a sexual stage specific gene (pfmdv 1) that is expressed substantially at a lower level in the Dd2 than in W2 parasite. Disruption of pfmdv 1 results in a dramatic reduction in mature gametocytes, especially male gametocytes, with the majority of sexually committed parasites arrested at stage-I. The pfmdv-1 knockout parasites show an enlarged nucleus, often with separation of the inner and outer nuclear membranes and presence of multi-membrane vesicles in red blood cell cytoplasm. Mosquito infectivity of the knockout parasites is also greatly reduced, but not completely lost, suggesting presence of compensatory mechanisms in the sexual development pathways. Data include Day 8 gametocytes of male defective Dd2 and parental W2 clones of Plasmodium falciparum. The series includes three biological repeats. Keywords: repeat sample
2005-05-01 | GSE2265 | GEO
Project description:The sexual stages are vital phases in malaria parasite transmission and are the targets of various interventions such as transmission blocking vaccines. The molecular mechanisms underlying sexual development, however, remain poorly understood. We report mappping of a determinant previously linked to a male gametocyte development defect in the P. falciparum Dd2 parasite to an 82 kb region on chromosome 12. In order to find a critical gene in this region, we compared gene expression pattern in sexual stage of the parasite between Dd2 and its normal gametocyte-producing ancestor W2 clones. The region contains a sexual stage specific gene (pfmdv 1) that is expressed substantially at a lower level in the Dd2 than in W2 parasite. Disruption of pfmdv 1 results in a dramatic reduction in mature gametocytes, especially male gametocytes, with the majority of sexually committed parasites arrested at stage-I. The pfmdv-1 knockout parasites show an enlarged nucleus, often with separation of the inner and outer nuclear membranes and presence of multi-membrane vesicles in red blood cell cytoplasm. Mosquito infectivity of the knockout parasites is also greatly reduced, but not completely lost, suggesting presence of compensatory mechanisms in the sexual development pathways. Data include Day 8 gametocytes of male defective Dd2 and parental W2 clones of Plasmodium falciparum. The series includes three biological repeats. Keywords: repeat sample
2010-06-10 | E-GEOD-2265 | biostudies-arrayexpress
Project description:The Apicomplexa constitute a large phylum of parasitic protozoans with complex life cycles that typically include meiotic sex. The life cycle of the malaria parasite, Plasmodium falciparum, includes obligate transition and stage development between a human and mosquito host. Asexual parasite replication in the human erythrocytes is followed by differentiation which leads to the formation of a precursor gamete stage, referred to as gametocytes. The gametocyte stage is solely responsible for malaria transmission into the mosquito vector where gamete fusion followed by meiosis occurs. How the parasite differentiates into male and female gametocytes in the absence of sex chromosomes largely remains an open question. Here, we combine FACS-based cell enrichment of a gametocyte reporter line followed by single-cell RNA-seq, to enable targeted characterization of the entire gametocyte developmental stage. Our data defines differential transcription programs during male and female gametocyte development and highlights a bifurcation point for sexual cell fate. We perform prediction analyses of novel candidate driver genes underlying P. falciparum sexual cell fate. Additionally, we delineate the timing of expression of members of the ApiAP2 family of transcription factors and predict their specificity in male or female P. falciparum gametocyte development.
2024-05-31 | GSE226145 | GEO
Project description:Plasmodium, the malaria parasite, undergoes a complex life cycle, which alternates between a vertebrate host and a mosquito vector of the genus Anopheles. In red blood cells of the vertebrate host, Plasmodium multiplies asexually or differentiates into gamete precursors, the male and female gametocytes, responsible for parasite transmission. Sexual stage maturation occurs in the midgut of the mosquito vector, where male and female gametes egress from the host erythrocyte to form a zygote. Gamete egress entails the successive rupture of two membranes surrounding the parasite, the parasitophorous vacuole membrane and the erythrocyte plasma membrane.
In this study, we applied a proteomic approach to identify proteins differentially released/secreted by female and male gametocytes of the rodent Plasmodium berghei activated to form gametes. We compared secreted molecules of the wild type gametocytes with those of a transgenic line defective in male gamete maturation and egress. This enabled us to provide a comprehensive dataset of egress-related molecules and their gender specificity. Using specific antibodies, we validated eleven candidate molecules, predicted as either gender-specific or common to both male and female gametocytes. All of them localize to punctuate, vesicle-like structures that relocate to cell periphery upon activation, but only three of them localize to the gametocyte-specific secretory vesicles named osmiophilic bodies. Our results confirm that the egress process involves a tightly coordinated secretory apparatus that includes different types of vesicles and may put the basis for functional studies aimed at designing novel transmission-blocking molecules.
2020-06-30 | MSV000085650 | MassIVE
Project description:The transmission of the malaria parasite between mosquitoes and mammals requires translational repression to ensure that only the proper proteins are expressed at the right time, while still allowing the parasite to prepare the mRNAs it will need for the next developmental stage. With relatively few known specific transcription factors (ApiAP2 family) that may specifically initiate gene transcription, Plasmodium parasites also regulate the stability and turnover of transcripts to provide more comprehensive gene regulation. The CAF1/CCR4/NOT complex has been shown in model organisms to be important for not only mRNA degradation, but also translational control through its deadenylases CAF1 and CCR4. However, few proteins that impose translational repression in Plasmodium sexual stages are known, and those that are characterized primarily affect female gametocytes. Therefore, we have characterized two deadenylases and have uncovered their roles in transmission. We have identified and characterized CCR4-1, which we show plays a role in activating male gametocytes, stabilizing transcripts in gametocytes, and regulating host-to-vector transmission. We find that when ccr4-1 is genetically deleted, there is a loss in the coordination of male gametocyte activation and a reduction in the ability of the parasite to productively infect the mosquito, which is independent of its effect upon male activation. Comparative RNA-seq shows that the deletion of ccr4-1 affects many transcripts that are translationally repressed in females, are related to male gamete function, and/or are important for early mosquito stage development. In contrast, we found that genetic deletion of the major deadenylase Caf1 is lethal. However, we observed that expression of only the N-terminal Caf1 domain is permissive, yet prevents proper complex assembly and phenocopies the ccr4-1 deletion. We therefore conclude that the general and transmission-specialized deadenylases of the CAF1/CCR4/NOT complex play critical and intertwined roles in parasite growth and transmission.
2019-01-02 | GSE101484 | GEO
Project description:The investigation of spliceosomal processes is currently a topic of intense research in molecular biology. In the molecular mechanism of alternative splicing, a multi-protein–RNA complex – the spliceosome – plays a crucial role. To understand the biological processes of alternative splicing, it is essential to comprehend the biogenesis of the spliceosome.
In this paper, we propose the first abstract model of the regulatory assembly pathway of the human spliceosomal subunit U1. Using Petri nets, we describe its highly ordered assembly that takes place in a stepwise manner.
2024-10-31 | MODEL2410300001 | BioModels
Project description:Investigation of whole genome gene expression level changes in Plasmodium falciparum 3D7 delta-PfPuf2 mutant, compared to the wild-type strain 3D7. The mutation engineered into this strain render tanslational control. The mutants analyzed in this study are further described in Miao J, Li J, Fan Q, Li X, Li X, Cui L.2010. The Puf-family RNA-binding protein PfPuf2 regulates sexual development and sex differentiation in the malaria parasite Plasmodium falciparum. J Cell Sci. 123(7):1039-49 (PMID 20197405).
2012-07-06 | GSE39124 | GEO
Project description:Transmission of malaria parasites from humans to the mosquito vector exclusively relies on the sexual reproduction of the parasite within the mosquito blood meal. Upon ingestion, Plasmodium male gametocyte undergoes explosive development: within 10 minutes, it completes three rounds of genome replication and endomitosis, assembles eight axonemes, and emerges from the host red blood cell. The plant-like calcium-dependent protein kinase 4 (CDPK4) was previously shown to be essential for male gametogenesis placing this kinase as an attractive drug target to block malaria transmission. Here we have identified and resolved three distinct molecular functions of CDPK4 during male gametogenesis. Activity of a myristoylated isoform is first required up to 20 seconds after activation to load the Mini-Chromosome Maintenance complex onto origins of replication. This role is partially mediated by a conserved protein belonging to the SAPS-domain family which is involved in the G1 to S-phase transition in eukaryotes. At the same time, activity of myristoylated CDPK4 is required to phosphorylate a Plasmodium-specific microtubule-associated protein necessary for mitotic spindle assembly. Finally, activity of a short non-myristoylated isoform of CDPK4 is essential seconds prior to completion of cytokinesis and the activation of male gamete motility. This late role has been linked to another Plasmodium-specific protein that is incorporated into axonemes during gametogenesis. This study reveals how a kinase of a protist parasite integrates and transduces multiple signals with a high spatiotemporal resolution to control both evolutionarily conserved and Plasmodium-specific biological processes.
2017-05-24 | PXD005884 | Pride