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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Autores principales: Maneesh K. Singh, Giulliana Tessarin-Almeida, Barbara K. M. Dias, Pedro Scarpellli Pereira, Fahyme Costa, Jude M. Przyborski, Celia R. S. Garcia
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/56eac78196474ce4a12acb089a0710f1
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spelling 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)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle 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
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