A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage
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...
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2021
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oai:doaj.org-article:56eac78196474ce4a12acb089a0710f12021-12-02T10:49:23ZA nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage10.1038/s41598-021-81235-22045-2322https://doaj.org/article/56eac78196474ce4a12acb089a0710f12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81235-2https://doaj.org/toc/2045-2322Abstract 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.Maneesh K. SinghGiulliana Tessarin-AlmeidaBarbara K. M. DiasPedro Scarpellli PereiraFahyme CostaJude M. PrzyborskiCelia R. S. GarciaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021) |
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Medicine R Science Q Maneesh K. Singh Giulliana Tessarin-Almeida Barbara K. M. Dias Pedro Scarpellli Pereira Fahyme Costa Jude M. Przyborski Celia R. S. Garcia A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage |
description |
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. |
format |
article |
author |
Maneesh K. Singh Giulliana Tessarin-Almeida Barbara K. M. Dias Pedro Scarpellli Pereira Fahyme Costa Jude M. Przyborski Celia R. S. Garcia |
author_facet |
Maneesh K. Singh Giulliana Tessarin-Almeida Barbara K. M. Dias Pedro Scarpellli Pereira Fahyme Costa Jude M. Przyborski Celia R. S. Garcia |
author_sort |
Maneesh K. Singh |
title |
A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage |
title_short |
A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage |
title_full |
A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage |
title_fullStr |
A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage |
title_full_unstemmed |
A nuclear protein, PfMORC confers melatonin dependent synchrony of the human malaria parasite P. falciparum in the asexual stage |
title_sort |
nuclear protein, pfmorc confers melatonin dependent synchrony of the human malaria parasite p. falciparum in the asexual stage |
publisher |
Nature Portfolio |
publishDate |
2021 |
url |
https://doaj.org/article/56eac78196474ce4a12acb089a0710f1 |
work_keys_str_mv |
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