Over-expression of Plasmodium G-actin binding proteins reveals a critical role for actin turnover in sporozoite transmission

YUKO SATO; MARION HLISCS; GEORGINA N. MONTAGNA; KAI MATUSCHEWSKI

WOODS HOLE

Congreso; Molecular Parasitology Meeting MPM XXVII; 2014

Plasmodium rely on actin-based motility to migrate from the site of infectionand invade target cells. With a substrate-dependent gliding locomotion,sporozoites are able to move at fast speed (1-3μm/s) with a minimal set ofproteins and in the absence of detectable elongated filamentous actin. Toinvestigate the molecular mechanism of gliding motility, two vital G-actin bidingproteins, C-CAP (C-terminal homology domain of adenylate cyclase-associatedprotein) and profilin, were over-expressed in merozoites, oookinetes, andsporozoites employing two stage-specific promoters. We show that inmerozoites and ookinetes, where both G-actin binding proteins are abundantlyexpressed, additional expression does not impair life cycle progression. Inmarked contrast, over-expression in immature and mature sporozoites ablatedcircular gliding motility, salivary gland invasion and transmission to themammalian host. Intracellular actin I distribution in sporozoites over-expressingC-CAP and profilin resembled immature non-motile sporozoites. We suggestthat actin turnover regulation is particularly tight in sporozoites, where fast andcontinuous locomotion is central to successful transmission and host switch.