Regulation of sexual differentiation is linked to invasion in malaria parasites
Regulation of sexual differentiation is linked to invasion in malaria parasites
Summary In the malaria parasite Plasmodium falciparum, the switch from asexual multiplication to sexual differentiation into gametocytes is essential for transmission to mosquitos. One of the key determinants of sexual commitment is the transcription factor PfAP2-G, which has been proposed to orchestrate this crucial cell fate decision by driving expression of gametocyte genes. We show conclusively that PfAP2-G is a transcriptional activator of gametocyte genes and identify the earliest known markers expressed during commitment. Remarkably, we also find that in sexually committed cells, PfAP2-G is associated with the promoters of genes important for red blood cell invasion and activates them through its interactions with a second transcription factor. We thus demonstrate an intriguing transcriptional link between the apparently opposing processes of red blood cell invasion and gametocytogenesis that is coordinated by the master regulator PfAP2-G. This finding has important implications for the development of new anti-malarial drugs that block the invasion of red blood cells by sexually committed cells, thereby preventing parasite transmission.
Josling Gabrielle A.、Orchard Lindsey、Painter Heather J.、Llin¨￠s Manuel、Russell Timothy J.、Venezia Jarrett
Department of Biochemistry and Molecular Biology, The Pennsylvania State University||Huck Center for Malaria Research, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University||Huck Center for Malaria Research, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University||Huck Center for Malaria Research, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University||Huck Center for Malaria Research, The Pennsylvania State University||Department of Chemistry, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University||Huck Center for Malaria Research, The Pennsylvania State UniversityDepartment of Biochemistry and Molecular Biology, The Pennsylvania State University||Huck Center for Malaria Research, The Pennsylvania State University||W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University
基础医学分子生物学微生物学
Josling Gabrielle A.,Orchard Lindsey,Painter Heather J.,Llin¨￠s Manuel,Russell Timothy J.,Venezia Jarrett.Regulation of sexual differentiation is linked to invasion in malaria parasites[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/533877.点此复制
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