Abstract
BackgroundGliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. Effective motility is dependent on a parasite myosin motor and turnover of dynamic parasite actin filaments. To date, however, the basis for directional motility is not known. Whilst myosin is very likely orientated as a result of its anchorage within the parasite, how actin filaments are orientated to facilitate directional force generation remains unexplained. In addition, recent evidence has questioned the linkage between actin filaments and secreted surface antigens leaving the way by which motor force is transmitted to the extracellular milieu unknown. Malaria parasites possess a markedly reduced repertoire of actin regulators, among which few are predicted to interact with filamentous (F)-actin directly. One of these, PF3D7_1251200, shows strong homology to the coronin family of actin-filament binding proteins, herein referred to as PfCoronin.MethodsHere the N terminal beta propeller domain of PfCoronin (PfCor-N) was expressed to assess its ability to bind and bundle pre-formed actin filaments by sedimentation assay, total internal reflection fluorescence (TIRF) microscopy and confocal imaging as well as to explore its ability to bind phospholipids. In parallel a tagged PfCoronin line in Plasmodium falciparum was generated to determine the cellular localization of the protein during asexual parasite development and blood-stage merozoite invasion.ResultsA combination of biochemical approaches demonstrated that the N-terminal beta-propeller domain of PfCoronin is capable of binding F-actin and facilitating formation of parallel filament bundles. In parasites, PfCoronin is expressed late in the asexual lifecycle and localizes to the pellicle region of invasive merozoites before and during erythrocyte entry. PfCoronin also associates strongly with membranes within the cell, likely mediated by interactions with phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) at the plasma membrane.ConclusionsThese data suggest PfCoronin may fulfil a key role as the critical determinant of actin filament organization in the Plasmodium cell. This raises the possibility that macro-molecular organization of actin mediates directional motility in gliding parasites.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0801-5) contains supplementary material, which is available to authorized users.
Highlights
Gliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell
In summary, evidence is presented demonstrating actin filament bundling by PfCoronin in vitro that, combined with in vivo imaging data and phospholipid binding, supports a role for PfCoronin being an important effector for organizing actin filaments in the invasive malaria parasite
If validated this would open up the possibility that Coronin across apicomplexan parasites, and across Plasmodium life cycle stages, may be a key organizing force for directional actin filaments and by extension gliding motility in these key human pathogens
Summary
Gliding motility in Plasmodium parasites, the aetiological agents of malaria disease, is mediated by an actomyosin motor anchored in the outer pellicle of the motile cell. Current models predict that this structure is composed of a single headed myosin motor, anchored between the IMC and plasma membrane via a series of binding partners [5]. The linkage between actin filaments and the terminal residues of surface-bound adhesins was thought to involve the glycolytic enzyme fructose 1,6 bisphosphate aldolase [7], which is known to bind actin [8]. According to this model, directional passage of the actin-aldolase-adhesin complex rearwards by the myosin motor would generate rearward force driving the parasite forwards
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