An inner membrane complex protein IMC1g in Plasmodium berghei plays an essential role in asexual erythrocytic proliferation and transmission
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PROVIDER: PRJNA1124569 | ENA |
REPOSITORIES: ENA
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Project description:Plasmodium berghei transcriptome for female gametocytes, male gametocytes, and asexual erythrocytic stages
2017-08-21 | GSE102167 | GEO
Project description:The inner membrane complex (IMC), a double-membrane organelle underneath the plasma membrane in apicomplexan parasites, plays a significant role in motility and invasion and confers shape to the cell. We characterized the function of PbIMC1g, a component of the IMC1 family member in Plasmodium berghei. PbIMC1g is recruited to the IMC in late schizonts, activated gametocytes, and ookinetes. Pairwise yeast two-hybrid assays demonstrate that PbIMC1g interacts with IMC1c, a component of the PHIL1 complex, and the core sub-repeat motif ‘EKI(V)V(I)EVP’ in PbIMC1g is essential for this interaction. Localization of PbIMC1g to the IMC was dependent on its IMCp domain, while its C-terminus and palmitoylation sites were required for the full efficiency of proper IMC targeting. PbIMC1g is required for asexual stage development, and its conditional knockdown resulted in a defect in schizogony. Additionally, PbIMC1g was also important for male gametogenesis and ookinete development. As an IMC component that assists in anchoring the glideosome to the subpellicular network, PbIMC1g was also involved in ookinete motility and mosquito midgut invasion. IMC1g from the human parasite P. Plasmodium vivax could functionally replace PbIMC1g in P. berghei, confirming the evolutionary conservation of IMC1g proteins in Plasmodium spp. Together, this work reveals an essential role of IMC1g in the parasite life cycle and suggests that IMC1 family members likely contribute to parasite gliding and invasion.
2024-11-06 | GSE269994 | GEO
Project description:The essential and distinct functions of Protein Phosphatase type 1 (PP1) catalytic subunit in eukaryotes are exclusively achieved through its interaction with a myriad of regulatory partners. In this work, we report the molecular and functional characterization of Gametocyte EXported Protein 15 (GEXP15), a Plasmodium specific protein, as a regulator of PP1. In vitro interaction studies demonstrated that GEXP15 physically interacts with PP1 through the RVxF binding motif in P. falciparum and P. berghei. Functional assays showed that GEXP15 was able to increase the PP1 activity and the mutation of the RVxF motif completely abolished this regulation. Immunoprecipitation assays of tagged GEXP15 or PP1 in P. berghei followed by immunoblot or mass spectrometry analyses confirmed their interaction and showed that they are present both in schizont and gametocyte stages in shared protein complexes involved in the spliceosome and proteasome pathways and known to play essential role in parasite development. Phenotypic analysis of viable GEXP15 deficient P. berghei blood parasites showed that they were unable to develop lethal infection in BALB/c mice or to establish experimental cerebral malaria in C57BL/6 mice. Further, although deficient parasites produced gametocytes they did not produce any oocysts/sporozoites indicating a high fitness cost in the mosquito. Global proteomic and phosphoproteomic analyses of GEXP15 deficient schizonts revealed a profound defect with a significant decrease in the abundance and an impact on phosphorylation status of proteins involved in regulation of gene expression or invasion. Moreover, the depletion of GEXP15 seemed to impact mainly the abundance of some specific proteins of female gametocytes. Our study provides the first insight into the contribution of a PP1 regulator to Plasmodium virulence and suggests that GEXP15 affects both the asexual and sexual life cycle.
2019-07-16 | PXD013874 | Pride
Project description:Proteomic characterization of complexity and dynamics of detergent resistant membranes of sexual and asexual stages of the rodent malaria parasite Plasmodium berghei
2016-08-31 | MSV000080108 | MassIVE
Project description:Phosphatase type 1 is a major enzyme essential to Plasmodium development. However, the detailed mechanisms underlying its regulation remain to be deciphered. In this work, we report the functional characterization of the Plasmodium berghei LRR1, an ortholog of SDS22, one of the most ancient and conserved Phosphatase type 1 (PP1) interactor. SDS22 has been described as a PP1 regulator essential to critical cellular features such as motility, polarity, epithelium integrity or mitosis completion. Our study shows that in Plasmodium berghei, PbLRR1 is expressed during the intra-erythrocytic developmental cycle and up to the zygote stage during sexual development. PbLRR1 can be found in complex with PbPP1 in both asexual and sexual stages and is able to inhibit the phosphatase activity. Then, genetic analysis demonstrated that PbLRR1 deletion affects the course of the parasite development during early sporogony which manifest by the production of fewer and smaller oocysts. Finally, PbLRR1 interactome analysis associated with phospho-proteomics studies led to the identification of several putative PbLRR1/PbPP1 substrates. Although previously unsuspected PP1 substrates, some of them have been characterized as essential to the parasite sexual development. In addition, and for the first time, we identify the PP1 inhibitor 3 as a substrate of the PP1/LRR1 complex. In summary, this study provides insights into previously unrecognized PbPP1 fine regulation of Plasmodium early sporogony development through its interaction with PbLRR1.
2022-10-14 | PXD030389 | Pride
Project description:The transmission of the malaria parasite between mosquitoes and mammals requires translational repression to ensure that only the proper proteins are expressed and correct folded at the right time, it will need for the next developmental stage.Due to their essential role for malaria transmission, gametocytes represent prime targets for transmission-blocking strategies intended to prevent spread of the deadly disease. In this study, we generate HspJ62 gene knockout line (ΔHspJ62) that is gametocyte non-producing lines. Transcriptional profiling of wild type Plasmodium berghei and genetic KO Hspj62 genes at single time points during erythrocytic parasite development.
2021-12-15 | GSE168974 | GEO
Project description:To identify protein phosphatases (PP) that are essential during asexual blood stage development in Plasmodium berghei, we attempted systematic deletion of the 30 P. berghei PP genes using double homologous recombination. Of these, we performed strand-specific RNA-sequencing (RNA-Seq) analysis for 2 myristoylated PP mutants _ppm2 and _ppm5 lines across relevant lifestages ( activated gametocyte and schizont stages in both _ppm2 and _ppm5 and ookinete stage in _ppm5 alone). Two to four biological replicates each for _ppm2, _ppm5 and wild-type parasites were processed into strand-specific RNA-seq libraries and sequenced in Illumina Hiseq platform using 100-bp paired end chemistry.
2014-04-16 | E-MTAB-2215 | biostudies-arrayexpress
Project description:During the malaria infection, Plasmodium parasites invade the host’s red blood cells where they can differentiate into two different life forms. The majority will replicate asexually and infect new erythrocytes. A small percentage, however, will transform into gametocytes – a specialized sexual stage able to survive and develop when taken up by Anopheles mosquito. As the gametocytes ensure the parasite’s transmission to a new host, their generation is an attractive target for new antimalarial interventions. The molecular mechanisms controlling gametocytogenesis, however, remain largely unknown due to the technical challenges: the early gametocytes are morphologically indistinguishable from asexual parasites and present in very low numbers during the infection. Recently, AP2-G - a transcription factor from an apicomplexa-specific apiAP2 family – was described as indispensable for gametocyte commitment in both human malaria parasite Plasmodium falciparum and rodent malaria model Plasmodium berghei. Therefore, we have decided to test whether the overexpression of this factor alone could increase gametocyte production and enable the investigation of uncharacterised, earliest stages of gametocyte development. To this end, we have engineered PBGAMi - a Plasmodium berghei line, in which all parasites were ap2-g deficient by default but able to overexpress it when induced with rapamycin. While the control parasites (PBGAMi R-), as expected, differentiated into asexual forms (schizonts) only, almost all rapamycin-treated parasites (PBGAMi R+) transformed into gametocytes. We used the generated line to perform RNA-seq analysis of the R- and R+ populations at different time points of their development and identify the changes arising between them, mapping the sequence of events leading to the formation of gametocytes.
2018-06-30 | GSE110201 | GEO