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Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization
by
Eri Saki H Hayakawa
, Inaoka, Daniel Ken
, Yoshida, Minako
, Tokumasu, Fuyuki
, Shindou, Hideo
, Sakura, Takaya
, Usukura, Jiro
, Tokuoka, Suzumi M
, Miyazaki, Shinya
, Kita, Kiyoshi
, Fukumoto, Junpei
in
Acyltransferase
/ Cell cycle
/ Cell membranes
/ Developmental stages
/ DNA biosynthesis
/ Internalization
/ Lipid composition
/ Malaria
/ Mass spectroscopy
/ Microbiology
/ Parasitemia
/ Parasites
/ Phospholipids
/ Plasmodium falciparum
/ Replication
/ Transcriptomics
/ Vacuoles
2024
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Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization
by
Eri Saki H Hayakawa
, Inaoka, Daniel Ken
, Yoshida, Minako
, Tokumasu, Fuyuki
, Shindou, Hideo
, Sakura, Takaya
, Usukura, Jiro
, Tokuoka, Suzumi M
, Miyazaki, Shinya
, Kita, Kiyoshi
, Fukumoto, Junpei
in
Acyltransferase
/ Cell cycle
/ Cell membranes
/ Developmental stages
/ DNA biosynthesis
/ Internalization
/ Lipid composition
/ Malaria
/ Mass spectroscopy
/ Microbiology
/ Parasitemia
/ Parasites
/ Phospholipids
/ Plasmodium falciparum
/ Replication
/ Transcriptomics
/ Vacuoles
2024
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Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization
by
Eri Saki H Hayakawa
, Inaoka, Daniel Ken
, Yoshida, Minako
, Tokumasu, Fuyuki
, Shindou, Hideo
, Sakura, Takaya
, Usukura, Jiro
, Tokuoka, Suzumi M
, Miyazaki, Shinya
, Kita, Kiyoshi
, Fukumoto, Junpei
in
Acyltransferase
/ Cell cycle
/ Cell membranes
/ Developmental stages
/ DNA biosynthesis
/ Internalization
/ Lipid composition
/ Malaria
/ Mass spectroscopy
/ Microbiology
/ Parasitemia
/ Parasites
/ Phospholipids
/ Plasmodium falciparum
/ Replication
/ Transcriptomics
/ Vacuoles
2024
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Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization
Paper
Pivotal roles of Plasmodium falciparum lysophospholipid acyltransferase 1 in cell cycle progression and cytostome internalization
2024
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Overview
The rapid intraerythrocytic replication of Plasmodium falciparum, a deadly species of malaria parasite, requires a quick but constant supply of phospholipids to support marked cell membrane expansion. In the malarial parasite, many enzymes functioning in phospholipid synthesis pathway have not been identified or characterized. Here, we identified P. falciparum lysophospholipid acyltransferase 1 (PfLPLAT1; PF3D7_1444300) and showed that PfLPLAT1 is vital for asexual parasite cell cycle progression and cytostome internalization. Deficiency in PfLPLAT1 resulted in decreased parasitemia and prevented transition to the schizont stage. Parasites lacking PfLPLAT1 also exhibited distinctive omega-shaped vacuoles, indicating disrupted cytostome function. Transcriptomic analyses suggested that this deficiency impacted DNA replication and cell cycle regulation. Mass spectrometry-based enzyme assay and lipidomic analysis demonstrated that recombinant PfLPLAT1 exhibited lysophospholipid acyltransferase activity with a preference for unsaturated fatty acids as its acyl donors and lysophosphatidic acids as an acceptor, with its conditional knockout leading to abnormal lipid composition and marked morphological and developmental changes including stage arrest. These findings highlight PfLPLAT1 as a potential target for antimalarial therapy, particularly due to its unique role and divergence from human orthologs.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Author's affilations were revised.
Publisher
Cold Spring Harbor Laboratory Press,Cold Spring Harbor Laboratory
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