Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission (Published Correction Nat Commun 2022 Aug 23;13(1):4944. https://www.nature.com/articles/s41467-022-32664-8)
- Author(s)
- Lopaticki, S; McConville, R; John, A; Geoghegan, N; Mohamed, SD; Verzier, L; Steel, RWJ; Evelyn, C; O'Neill, MT; Soler, NM; Scott, NE; Rogers, KL; Goddard-Borger, ED; Boddey, JA;
- Details
- Publication Year 2022-07-29,Volume 13,Issue #1,Page 4400
- Journal Title
- Nature Communications
- Abstract
- Tryptophan C-mannosylation stabilizes proteins bearing a thrombospondin repeat (TSR) domain in metazoans. Here we show that Plasmodium falciparum expresses a DPY19 tryptophan C-mannosyltransferase in the endoplasmic reticulum and that DPY19-deficiency abolishes C-glycosylation, destabilizes members of the TRAP adhesin family and inhibits transmission to mosquitoes. Imaging P. falciparum gametogenesis in its entirety in four dimensions using lattice light-sheet microscopy reveals defects in ΔDPY19 gametocyte egress and exflagellation. While egress is diminished, ΔDPY19 microgametes still fertilize macrogametes, forming ookinetes, but these are abrogated for mosquito infection. The gametogenesis defects correspond with destabilization of MTRAP, which we show is C-mannosylated in P. falciparum, and the ookinete defect is concordant with defective CTRP secretion on the ΔDPY19 background. Genetic complementation of DPY19 restores ookinete infectivity, sporozoite production and C-mannosylation activity. Therefore, tryptophan C-mannosylation by DPY19 ensures TSR protein quality control at two lifecycle stages for successful transmission of the human malaria parasite.
- Publisher
- NPG
- Research Division(s)
- Chemical Biology; Advanced Technology And Biology; Infectious Diseases And Immune Defence
- PubMed ID
- 35906227
- Publisher's Version
- https://doi.org/10.1038/s41467-022-32076-8
- Open Access at Publisher's Site
https://doi.org/10.1038/s41467-022-32076-8 - NHMRC Grants
- NHMRC/GNT1139546, NHMRC/GNT1123727,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2022-08-08 09:15:54
Last Modified: 2022-08-25 08:57:57