Transcriptome and histone epigenome of<i>Plasmodium vivax</i>salivary-gland sporozoites point to tight regulatory control and potential mechanisms for liver-stage differentiation

Müller, Ivan; Ar, Jex; Sh, I. Kappe; Sa, Mikolajczak; Sattabongkot, Jetsumon; Patrapuvich, Rapatbhorn; Lindner, Scott E.; El, Flannery; Koepfli, Cristian; Ansell, Brendan R E; Lerch, Anita; Sj, Emery-Corbin; Charnaud, Sarah C.; Smith, Jeffrey S.; Merrienne, Nicolas; Ke, Swearingen; Rl, Moritz; Petter, Michaela; Duffy, Michael; Chuenchob,

doi:10.1101/145250

Cited by 3 publications

(1 citation statement)

References 78 publications

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“…AP2-L (subcluster 1), which is typically expressed in the sporozoites and trophozoites of P. falciparum and P. berghei, is the only known stage-specific TF involved in parasite liver infection [80,81]. P. vivax has also been shown to exhibit high transcript levels in sporozoites [82]. When sporozoites enter the liver, AP2-L aids in their proper growth into the hepatic stage.…”

Section: Stage-specific Transcriptome Of P Bergheimentioning

confidence: 99%

Transcriptome analysis reveals a novel DNA element that may interact with chromatin-associated proteins inPlasmodium bergheiduring erythrocytic development

Okafor,

Adam,

Brors

et al. 2024

Preprint

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Background: The life cycle of Plasmodium parasites is intricate and multistage, alternating between dynamic environments. Temporal regulation of transcription by stage-specific transcription factor binding at particular regulatory regions within gene promoters facilitates its progression. As a result, each new developmental stage is endowed with its unique gene sets, whose just-in-time expression enables the parasite to completely adapt to the necessary circumstances. Our understanding of these transcriptome-level regulatory processes is limited, and more so, a thorough examination of the entire life cycle in the experimentally tractable rodent model organism P. berghei is lacking. Results: We performed a genome-wide analysis of RNA-Seq data from different developmental stages of P. berghei. Integrated data from the human malaria parasites P. falciparum and P. vivax demonstrated that Plasmodium parasites have a unique transcriptional signature. We identified the sets of genes differentially expressed at each stage, clustered them based on similarities of their expression profiles, and predicted the regulatory motifs governing their expression. We interpreted the motifs using known binding sites for established eukaryotic transcription factors, including those of the ApiAP2s, and identified eight potentially novel motifs. Additionally, we expanded the annotation of another motif, AGGTAA, found in genes exclusive to erythrocytic development and identified members of the PfMORC and GCN5 complexes among its possible interacting proteins. Conclusion: This study provides new insights into gene usage and its regulation during P. berghei development. Keywords: Plasmodium berghei, RNA-Seq, ApiAP2s, regulatory motifs, Plasmodium falciparum, Plasmodium vivax

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Section: Stage-specific Transcriptome Of P Bergheimentioning

confidence: 99%

Transcriptome analysis reveals a novel DNA element that may interact with chromatin-associated proteins inPlasmodium bergheiduring erythrocytic development

Okafor,

Adam,

Brors

et al. 2024

Preprint

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Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP

Steel

Вигдорович

Dambrauskas

et al. 2021

Sci Rep

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Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.

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Platelet Derived Growth Factor Receptor β (PDGFRβ) is a Host Receptor for the human malaria parasite adhesin TRAP

Steel¹,

Вигдорович²,

Dambrauskas³

et al. 2020

Preprint

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Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion mutants showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax , but not the rodent-infective parasite Plasmodium yoelii . We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.

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Transcriptome and histone epigenome ofPlasmodium vivaxsalivary-gland sporozoites point to tight regulatory control and potential mechanisms for liver-stage differentiation

Cited by 3 publications

References 78 publications

Transcriptome analysis reveals a novel DNA element that may interact with chromatin-associated proteins inPlasmodium bergheiduring erythrocytic development

Transcriptome analysis reveals a novel DNA element that may interact with chromatin-associated proteins inPlasmodium bergheiduring erythrocytic development

Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP

Platelet Derived Growth Factor Receptor β (PDGFRβ) is a Host Receptor for the human malaria parasite adhesin TRAP

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