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A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation

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Title: A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation
Authors: Ishizaki, Takahiro / Chaiyawong, Nattawat / Hakimi, Hassan / Asada, Masahito / Tachibana, Mayumi / Ishino, Tomoko / Yahata, Kazuhide / Kaneko, Osamu
Issue Date: 14-Jan-2020
Publisher: Elsevier B.V.
Citation: Parasitology International, 76, art.no.102056; 2020
Abstract: Malaria parasites proliferate by repeated invasion of and multiplication within erythrocytes in the vertebrate host. Sexually committed intraerythrocytic parasites undergo sexual stage differentiation to become gametocytes. After ingestion by the mosquito, male and female gametocytes egress from erythrocytes and fertilize within the mosquito midgut. A complex signaling pathway likely responds to environmental events to trigger gametogenesis and regulate fertilization; however, such knowledge remains limited for malaria parasites. Several pseudokinases are highly transcribed at the gametocyte stage and are possible multi-functional regulators controlling critical steps of the life cycle. Here we characterized one pseudokinase, termed PypPK1, in Plasmodium yoelii that is highly expressed in schizonts and male gametocytes. Immunofluorescence assays for parasites expressing Myc-tagged PypPK1 confirmed that PypPK1 protein is expressed in schizonts and sexual stage parasites. Transgenic ΔpPK1 parasites, in which the PypPK1 gene locus was deleted by the CRISPR/Cas9 method, showed significant growth defect and reduced virulence in mice. In the blood stage, ΔpPK1 parasites were able to egress from erythrocytes similar to wild type parasites; however, erythrocyte invasion efficacy was significantly reduced. During sexual stage development, no clear changes were seen in male and female gametocytemias as well as gametocyte egress from erythrocytes; but, the number of exflagellation centers and oocysts were significantly reduced in ΔpPK1 parasites. Taken together, PypPK1 has an important role for both erythrocyte invasion and exflagellation center formation.
Keywords: Plasmodium yoelii / Pseudokinase / Exflagellation center / Sexual stage / Erythrocyte invasion / Malaria
URI: http://hdl.handle.net/10069/39655
ISSN: 13835769
DOI: 10.1016/j.parint.2020.102056
Rights: © 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license(http://creativecommons.org/licenses/BY/4.0/).
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/39655

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