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

Akanksha Rawat, Neelam Antil, Meenakshi, Bhagyashree Deshmukh, Akhila Balakrishna Rai, Annu Nagar, Narendra Kumar, T. S. Keshava Prasad, Krishanpal Karmodiya and Pushkar Sharma ()
Additional contact information
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

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59476-w

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