Meiosis in Plasmodium: how does it work?

Guttery, David S.; Zeeshan, Mohammad; Holder, Anthony A.; Tromer, Eelco C.; Tewari, Rita

doi:10.1016/j.pt.2023.07.002

Cited by 4 publications

(2 citation statements)

References 43 publications

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“…Among the most abundant up-regulated zygote proteins are members of the LCCL-domain containing family (CCp and LAP (36, 37)), which are essential for the maturation of gametes and ookinetes. Unlike in typical metazoans, meiosis in Plasmodium occurs after fertilization (38), and accordingly, we detected key meiosis proteins in the zygote, including NEK4, DMC1, and RAD51. Additionally, we detect proteins required by early mosquito-stage parasites to become motile (IMC proteins and their regulators, CelTOS), adjust their surface protein composition (p25, p28, PSOPs, CPW-WPCs, CTRP, WARP, all known members of the crystalloid), develop the ability to evade mosquito immunity (P47, Cap380), and prepare for segmentation (basal complex members).…”

Section: Resultsmentioning

confidence: 67%

Global Release of Translational Repression AcrossPlasmodium’sHost-to-Vector Transmission Event

Rios,

McGee,

Sebastian

et al. 2024

Preprint

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Malaria parasites must be able to respond quickly to changes in their environment, including during their transmission between mammalian hosts and mosquito vectors. Therefore, before transmission, female gametocytes proactively produce and translationally repress mRNAs that encode essential proteins that the zygote requires to establish a new infection. This essential regulatory control requires the orthologues of DDX6 (DOZI), LSM14a (CITH), and ALBA proteins to form a translationally repressive complex in female gametocytes that associates with many of the affected mRNAs. However, while the release of translational repression of individual mRNAs has been documented, the details of the global release of translational repression have not. Moreover, the changes in spatial arrangement and composition of the DOZI/CITH/ALBA complex that contribute to translational control are also not known.Therefore, we have conducted the first quantitative, comparative transcriptomics and DIA-MS proteomics ofPlasmodiumparasites across the host-to-vector transmission event to document the global release of translational repression. Using female gametocytes and zygotes ofP. yoelii, we found that nearly 200 transcripts are released for translation soon after fertilization, including those with essential functions for the zygote. However, we also observed that some transcripts remain repressed beyond this point. In addition, we have used TurboID-based proximity proteomics to interrogate the spatial and compositional changes in the DOZI/CITH/ALBA complex across this transmission event. Consistent with recent models of translational control, proteins that associate with either the 5’ or 3’ end of mRNAs are in close proximity to one another during translational repression in female gametocytes and then dissociate upon release of repression in zygotes. This observation is cross-validated for several protein colocalizations in female gametocytes via ultrastructure expansion microscopy and structured illumination microscopy. Moreover, DOZI exchanges its interaction from NOT1-G in female gametocytes to the canonical NOT1 in zygotes, providing a model for a trigger for the release of mRNAs from DOZI. Finally, unenriched phosphoproteomics revealed the modification of key translational control proteins in the zygote. Together, these data provide a model for the essential translational control mechanisms used by malaria parasites to promote their efficient transmission from their mammalian host to their mosquito vector.

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Section: Resultsmentioning

confidence: 67%

Global Release of Translational Repression AcrossPlasmodium’sHost-to-Vector Transmission Event

Rios,

McGee,

Sebastian

et al. 2024

Preprint

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“…Ingestion in the blood meal by a mosquito activates the gametocytes, with male(micro) gametocytes undergoing three rounds of rapid DNA replication and mitosis without karyokinesis (termed endomitosis) within 15 min, followed by karyokinesis and cytokinesis leading to the budding of eight haploid gametes. These motile gametes find and fertilise the mature female(macro) gamete ( Figure 1A (ii)) to produce a diploid zygote [ 7 ], which over a period of 24 h elongates and differentiates into a crescent (or ‘banana’)-shaped motile ookinete, accompanied by DNA replication (to 4N) and the first stages of meiosis. The ookinete traverses the mosquito midgut wall and develops into an oocyst over a period of up to 21 days.…”

Section: Introductionmentioning

confidence: 99%

The molecular mechanisms driving Plasmodium cell division

Guttery,

Zeeshan,

Holder

et al. 2024

Biochemical Society Transactions

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Malaria, a vector borne disease, is a major global health and socioeconomic problem caused by the apicomplexan protozoan parasite Plasmodium. The parasite alternates between mosquito vector and vertebrate host, with meiosis in the mosquito and proliferative mitotic cell division in both hosts. In the canonical eukaryotic model, cell division is either by open or closed mitosis and karyokinesis is followed by cytokinesis; whereas in Plasmodium closed mitosis is not directly accompanied by concomitant cell division. Key molecular players and regulatory mechanisms of this process have been identified, but the pivotal role of certain protein complexes and the post-translational modifications that modulate their actions are still to be deciphered. Here, we discuss recent evidence for the function of known proteins in Plasmodium cell division and processes that are potential novel targets for therapeutic intervention. We also identify key questions to open new and exciting research to understand divergent Plasmodium cell division.

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