Comparative Plasmodium gene overexpression reveals distinct perturbation of sporozoite transmission by profilin

Yuko Sato, Marion Hliscs, Josefine Dunst, Christian Goosmann, Volker Brinkmann, Georgina N. Montagna, Kai Matuschewski

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Plasmodium relies on actin-based motility to migrate from the site of infection and invade target cells. Using a substrate-dependent gliding locomotion, sporozoites are able to move at fast speed (1-3 μm/s). This motility relies on a minimal set of actin regulatory proteins and occurs in the absence of detectable filamentous actin (F-Actin). Here we report an overexpression strategy to investigate whether perturbations of F-Actin steady-state levels affect gliding locomotion and host invasion. We selected two vital Plasmodium berghei G-Actin-binding proteins, C-CAP and profilin, in combination with three stage-specific promoters and mapped the phenotypes afforded by overexpression in all three extracellular motile stages. We show that in merozoites and ookinetes, additional expression does not impair life cycle progression. In marked contrast, overexpression of C-CAP and profilin in sporozoites impairs circular gliding motility and salivary gland invasion. The propensity for productive motility correlates with actin accumulation at the parasite tip, as revealed by combinations of an actin-stabilizing drug and transgenic parasites. Strong expression of profilin, but not C-CAP, resulted in complete life cycle arrest. Comparative overexpression is an alternative experimental genetic strategy to study essential genes and reveals effects of regulatory imbalances that are not uncovered from deletion-mutant phenotyping.

Original languageEnglish
Pages (from-to)2234-2244
Number of pages11
JournalMolecular biology of the cell
Volume27
Issue number14
DOIs
Publication statusPublished - 2016 Jul 15
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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