Journal Article PUBDB-2024-08033

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APEX-based proximity labeling in Plasmodium identifies a membrane protein with dual functions during mosquito infection

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2024
PLoS Lawrence, Kan.

PLoS pathogens 20(12), e1012788 () [10.1371/journal.ppat.1012788]
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Abstract: Transmission of the malaria parasite Plasmodium to mosquitoes necessitates gamete egress from red blood cells to allow zygote formation and ookinete motility to enable penetration of the midgut epithelium. Both processes are dependent on the secretion of proteins from distinct sets of specialized vesicles. Inhibiting some of these proteins has shown potential for blocking parasite transmission to the mosquito. To identify new transmission blocking vaccine candidates, we aimed to define the microneme content from ookinetes of the rodent model organism Plasmodium berghei using APEX2-mediated rapid proximity-dependent biotinylation. Besides known proteins of ookinete micronemes, this identified over 50 novel candidates and sharpened the list of a previous survey based on subcellular fractionation. Functional analysis of a first candidate uncovered a dual role for this membrane protein in male gametogenesis and ookinete midgut traversal. Mutation of a putative trafficking motif in the C-terminus affected ookinete to oocyst transition but not gamete formation. This suggests the existence of distinct functional and transport requirements for Plasmodium proteins in different parasite stages.

Classification:

Contributing Institute(s):
  1. CSSB-BNITM-TG (CSSB-BNITM-TG)
Research Program(s):
  1. 899 - ohne Topic (POF4-899) (POF4-899)
  2. DFG project G:(GEPRIS)240245660 - SFB 1129: Integrative Analyse der Replikation und Ausbreitung pathogener Erreger (240245660) (240245660)
  3. DFG project G:(GEPRIS)422048538 - SPP 2225: Wirtszellaustritt intrazellulärer Pathogene (422048538) (422048538)
Experiment(s):
  1. No specific instrument

Appears in the scientific report 2024
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 Record created 2024-12-20, last modified 2025-07-23


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