A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage

Author(s)

Singh, Maneesh K. ^{[1, 2]} ; Tessarin-Almeida, Giulliana ^[3] ; Dias, Barbara K. M. ^{[1, 2]} ; Pereira, Pedro Scarpellli ^{[1, 2]} ; Costa, Fahyme ^[1] ; Przyborski, Jude M. ^[4] ; Garcia, Celia R. S. ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508000 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst Biosci, Dept Physiol, BR-05508090 Sao Paulo - Brazil

^[4] Justus Liebig Univ, Dept Biochem & Mol Biol BiMoBi, Interdisciplinary Res Ctr iFZ, Giessen - Germany

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 11, n. 1 JAN 21 2021.
• Web of Science Citations: 1

Abstract

The host hormone melatonin is known to modulate the asexual cell-cycle of the human malaria parasite Plasmodium falciparum and the kinase PfPK7 is fundamental in the downstream signaling pathways. The nuclear protein PfMORC displays a histidine kinase domain and is involved in parasite cell cycle control. By using a real-time assay, we show a 24 h (h) rhythmic expression of PfMORC at the parasite asexual cycle and the expression is dramatically changed when parasites were treated with 100 nM melatonin for 17 h. Moreover, PfMORC expression was severely affected in PfPK7 knockout (PfPK7(-)) parasites following melatonin treatment. Parasites expressing 3D7(morc-GFP) shows nuclear localization of the protein during the asexual stage of parasite development. Although the PfMORC knockdown had no significant impact on the parasite proliferation in vitro it significantly changed the ratio of the different asexual intraerythrocytic stages of the parasites upon the addition of melatonin. Our data reveal that in addition to the upstream melatonin signaling pathways such as IP3 generation, calcium, and cAMP rise, a nuclear protein, PfMORC is essential for the hormone response in parasite synchronization. (AU)

• FAPESP's process: 17/08684-7 - Decoding Plasmodium signaling at molecular level as a new tool to the development of new antimalarials
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 19/09490-7 - Screening of novel ligands for PfSR1, a putative GPCR-like receptor and identification of potential IP3 receptor in calcium signaling in the Plasmodium falciparum
• Grantee: Maneesh Kumar Singh
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 11/51295-5 - Functional genomics in Plasmodium
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/07177-7 - EMU concedido no processo 2011/51295-5: image system
• Grantee: Célia Regina da Silva Garcia
• Support Opportunities: Multi-user Equipment Program