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Cited by 26Malaria Research and ControlGlycosylation and Glycoproteins ResearchTrypanosoma species research and implications

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Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission

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Lopaticki, Sash, McConville, Robyn, John, Alan, Geoghegan, Niall, Mohamed, Shihab Deen, Verzier, Lisa, Steel, Ryan W. J., Evelyn, Cindy, O’Neill, Matthew T., Soler, Niccolay Madiedo, Scott, Nichollas E., Rogers, Kelly L., Goddard-Borger, Ethan D., Boddey, Justin A.·2022·Nature Communications
DOI 10.1038/s41467-022-32076-8PMC PMC9338275

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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 Δ DPY19 gametocyte egress and exflagellation. While egress is diminished, Δ DPY19 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 Δ DPY19 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.

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Metadata

Authors
Lopaticki, S., McConville, R., John, A., Geoghegan, N., Mohamed, S. D., Verzier, L., Steel, R. W. J., Evelyn, C., O’Neill, M. T., Soler, N. M., Scott, N. E., Rogers, K. L., Goddard-Borger, E. D., & Boddey, J. A.
Affiliations
  • Walter and Eliza Hall Institute of Medical Research (AU)
  • The University of Melbourne (AU)
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-07-29
Volume
13
Issue
1
Pages
4400-4400
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-32076-8
PMC
PMC9338275
OpenAlex
W4288535357
Cited by
26
References
2
Citations by year
2026: 6 · 2025: 8 · 2024: 8 · 2023: 4
FWCI
4.41
Type
journal article
Language
en
Update notices
correction (2022-08-23)
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
Funders
  • Department of Education and Training | Australian Research Council (210100362)
  • Department of Health | National Health and Medical Research Council (GNT1123727, GNT1139546, 1176955)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Epidemiology › Trypanosoma species research and implications
Keywords
Plasmodium falciparum, gametogenesis, mosquito-borne transmission, protein stability, exflagellation, microgametes, endoplasmic reticulum
MeSH terms
Animals, Glycosylation, Humans, Culicidae, Plasmodium falciparum, Tryptophan, Protozoan Proteins, Malaria, Falciparum, Thrombospondins

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