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Molecular basis of synchronous replication of malaria parasites in the blood stage

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CURRENT OPINION IN MICROBIOLOGY
卷 63, 期 -, 页码 210-215

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CURRENT BIOLOGY LTD
DOI: 10.1016/j.mib.2021.08.002

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  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2017/08684-7, 2020/08988-9]

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The search for host factors leading to malaria parasite synchronization has been a focus of many laboratories. Melatonin has been identified as a key hormone that synchronizes Plasmodium falciparum in culture by increasing the number of mature parasite stages through PLC-IP3 activation. Melatonin signaling is linked to crosstalk between Ca2+-cAMP that results in PKA activation. Two other kinases and a nuclear protein are also identified as part of the hormone-signal transduction pathways.
The search for host factors that leads to malaria parasite synchronization has been the focus of several laboratories. The host hormone melatonin synchronizes Plasmodium falciparum in culture by increasing the number of mature parasite stages through a PLC-IP3 activation. Melatonin signaling is linked to crosstalk between Ca2+-cAMP that results in PKA activation. Two other kinases, PfPK7 and PfelK1, and the nuclear protein PfMORC that lacks melatonin sensitivity in the inducible knock-down parasites are also identified as part of the hormone-signal transduction pathways. Melatonin also modulates P. falciparum mitochondrial fission genes FIS1, DYN1, and DYN2 in a stage-specific manner. How these multiple molecular mechanisms are orchestrated to lead to parasite synchronization is a fascinating and opened biological question.

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