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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 11, n. 1 JAN 21 2021.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 17/08684-7 - Decodificar aspectos da biologia celular e molecular do Plasmodium como uma ferramenta para desenvolver novos antimaláricos
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 19/09490-7 - Triagem de ligantes para PfSR1, um provável receptor tipo GPCR, e identificação de um possível receptor de IP3 na sinalização de cálcio no Plasmodium falciparum
• Beneficiário: Maneesh Kumar Singh
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 11/51295-5 - Genômica funcional em Plasmodium
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/07177-7 - EMU concedido no processo 2011/51295-5: image system
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários