The Actin Filament-Binding Protein Coronin Regulates Motility in Plasmodium Sporozoites

Abstract

Parasites causing malaria need to migrate in order to penetrate tissue barriers and enter host cells. Here we show that the actin filament-binding protein coronin regulates gliding motility in Plasmodium berghei sporozoites, the highly motile forms of a rodent malaria-causing parasite transmitted by mosquitoes. Parasites lacking coronin show motility defects that impair colonization of the mosquito salivary glands but not migration in the skin, yet result in decreased transmission efficiency. In non-motile sporozoites low calcium concentrations mediate actin-independent coronin localization to the periphery. Engagement of extracellular ligands triggers an intracellular calcium release followed by the actin-dependent relocalization of coronin to the rear and initiation of motility. Mutational analysis and imaging suggest that coronin organizes actin filaments for productive motility. Using coronin-mCherry as a marker for the presence of actin filaments we found that protein kinase A contributes to actin filament disassembly. We finally speculate that calcium and cAMP-mediated signaling regulate a switch from rapid parasite motility to host cell invasion by differentially influencing actin dynamics.

Microstructured Blood Vessel Surrogates Reveal Structural Tropism of Motile Malaria Parasites

“…To this end we put midgutderived sporozoites into a set of pillar arrays and also investigated sporozoites lacking the actin filament binding protein coronin, which show defects in 2D but not in 3D motility. [27] However, neither of these sporozoite populations showed an increase of their migration capacity in the pillar arrays ( Figure 7). …”

“…These coronin(-) sporozoites move in the dermis similar to wild type sporozoites. [27] This suggests that the confinement of the dermal tissue is higher than that conferred by the pillar arrays.…”

“…These could interact with the sporozoite and slow it down even further by either increasing adhesion efficiency or by signaling. [22,27,36,37] This could be tested in pillar arrays or on flat substrates by linking the proteins covalently to the surface and comparing the speed of sporozoites gliding on these variable surfaces.…”

Gliding motility powers invasion and egress in Apicomplexa

“…berghei sporozoites 46 , whereas in T. gondii coronin relocalizes to the posterior pole of the parasite concomitantly to microneme secretion but does not affect motility 47 . Thus, actin polymerization is clearly important for the process of gliding motility in Apicomplexa.…”

A hybrid plasmid pGEM-pET28 applied for heterologous expression of Neospora caninum actin

“…Moreover, the reduction of the plasmid size improves transformation efficiency and stability in E. coli [13], a clear advantage of the pGEMpET28 compared to pET28. The importance of actin in Apicomplexa has been extensively demonstrated using T. gondii and Plasmodium models [14] [15]. The use of pGEM-pET28 allows future research involving actin of N. caninum, bringing further knowledge of this protein within the phylum and its role in the invasion process.…”