A 39-Amino-Acid C-Terminal Truncation of GDV1 Disrupts Sexual Commitment in Plasmodium falciparum

• DOI: 10.1128/msphere.01093-20
• Publication Date: 2021-05-18T13:51:33Z
• Authors: Marta Tibúrcio; Eva Hitz; Igor Niederwieser; Gavin Kelly; Heledd Davies; Christian Doerig; Oliver Billker; Till S. Voss; Moritz Treeck
• Keywords: Life Cycle Stages; 0303 health sciences; Sex Differentiation; Sequence Analysis, RNA; Plasmodium falciparum; Protozoan Proteins; Microbiology; QR1-502; Gametogenesis; 3. Good health; 03 medical and health sciences; Gene Expression Regulation; Humans; Amino Acids; Malaria, Falciparum; Research Article

Malaria is a mosquito-borne disease caused by apicomplexan parasites of the genus Plasmodium. Completion parasite's life cycle depends on transmission sexual stages, gametocytes, from an infected human host to mosquito vector. Sexual commitment occurs in only small fraction asexual blood-stage and initiated external cues. The gametocyte development protein 1 (GDV1) has been described as key facilitator trigger commitment. GDV1 interacts with silencing factor heterochromatin (HP1), leading its dissociation heterochromatic DNA at genomic locus encoding AP2-G, master transcription gametocytogenesis. How this process regulated not known. In study, we have addressed role kinases implicated development. From pool available kinase knockout (KO) lines, identified two lines which fail produce gametocytes. However, independent genetic verification revealed that both are required for gametocytogenesis but harbor same mutation leads truncation extreme C terminus GDV1. Introduction nonsense into genome wild-type parasite replicates observed phenotype. Using overexpression line, show does interfere nuclear import or interaction HP1 vitro appears be important sustain levels thereby commitment.IMPORTANCE Transmission malaria-causing Plasmodium species mosquitos requires change continuously growing form blood sexually differentiated form, gametocyte. Only subset differentiates gametocytes taken up mosquito. represents bottleneck parasite, so molecular understanding events lead stage conversion may identify novel intervention points. Here, screened hypothesized play process. While did conversion, (GDV1), abrogates destabilizes cognate binding partner HP1. This suggests beyond trafficking stability.