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PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum

Author

Listed:
  • Akanksha Rawat

    (Aruna Asaf Ali Marg)

  • Neelam Antil

    (Yenepoya (Deemed to be University))

  • Meenakshi

    (Aruna Asaf Ali Marg)

  • Bhagyashree Deshmukh

    (Pashan)

  • Akhila Balakrishna Rai

    (Yenepoya (Deemed to be University))

  • Annu Nagar

    (Aruna Asaf Ali Marg)

  • Narendra Kumar

    (National Institute of Immunology)

  • T. S. Keshava Prasad

    (Yenepoya (Deemed to be University))

  • Krishanpal Karmodiya

    (Pashan)

  • Pushkar Sharma

    (Aruna Asaf Ali Marg)

Abstract

Malaria parasite undergoes interesting developmental transition in human and mosquito host. While it divides asynchronously in the erythrocytes, it switches to sexual forms, which is critical for disease transmission. We report a novel signalling pathway involving Protein Phosphatase PfPPM2, which regulates asexual division of Plasmodium falciparum as well as its conversion to sexual forms. PfPPM2 may regulate the phosphorylation of key proteins involved in chromatin remodelling and protein translation. One of the key PfPPM2-targets was Heterochromatin Protein 1 (HP1), a regulator of heritable gene silencing which contributes to both mitotic proliferation as well as sexual commitment of the parasite. PfPPM2 promotes sexual conversion by regulating the interaction between HP1, H3K9me3 and chromatin and it achieves this by dephosphorylating S33 of HP1. PfPPM2 also regulates protein synthesis in the parasite by repressing the phosphorylation of initiation factor eIF2α, which is likely to contribute to parasite division and possibly sexual differentiation.

Suggested Citation

  • Akanksha Rawat & Neelam Antil & Meenakshi & Bhagyashree Deshmukh & Akhila Balakrishna Rai & Annu Nagar & Narendra Kumar & T. S. Keshava Prasad & Krishanpal Karmodiya & Pushkar Sharma, 2025. "PfPPM2 signalling regulates asexual division and sexual conversion of human malaria parasite Plasmodium falciparum," Nature Communications, Nature, vol. 16(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59476-w
    DOI: 10.1038/s41467-025-59476-w
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    References listed on IDEAS

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    1. Sudhir Kumar & Manish Kumar & Roseleen Ekka & Jeffrey D. Dvorin & Aditya S. Paul & Anil K. Madugundu & Tim Gilberger & Harsha Gowda & Manoj T. Duraisingh & T. S. Keshava Prasad & Pushkar Sharma, 2017. "PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Mohammad Zeeshan & Edward Rea & Steven Abel & Kruno Vukušić & Robert Markus & Declan Brady & Antonius Eze & Ravish Rashpa & Aurelia C. Balestra & Andrew R. Bottrill & Mathieu Brochet & David S. Gutter, 2023. "Plasmodium ARK2 and EB1 drive unconventional spindle dynamics, during chromosome segregation in sexual transmission stages," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Andrew J. Bannister & Philip Zegerman & Janet F. Partridge & Eric A. Miska & Jean O. Thomas & Robin C. Allshire & Tony Kouzarides, 2001. "Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain," Nature, Nature, vol. 410(6824), pages 120-124, March.
    4. Gabrielle A. Josling & Timothy J. Russell & Jarrett Venezia & Lindsey Orchard & Riëtte Biljon & Heather J. Painter & Manuel Llinás, 2020. "Dissecting the role of PfAP2-G in malaria gametocytogenesis," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
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