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. Parasites causing malaria are transmitted by mosquitoes and need to migrate to cross tissue barriers. The form of the parasite transmitted by the mosquito, the so-called sporozoite, needs motility to enter the salivary glands, to migrate within the skin and to enter into blood capillaries and eventually hepatocytes, where the parasites differentiate into thousands of merozoites that invade red blood cells. Sporozoite motility is based on an actin-myosin motor, as is the case in many other eukaryotic cells. However, most eukaryotic cells move much slower than sporozoites. How these parasites reach their high speed is not clear but current evidence suggests that actin filaments need to be organized by either actin-binding proteins or membrane proteins that link the filaments to an extracellular substrate. The present study explores the role of the actin filament-binding protein coronin in the motility of sporozoites of the rodent model parasite Plasmodium berghei. We found that the deletion of P. berghei coronin leads to defects in parasite motility and thus lower infection of mosquito salivary glands, which translates into less efficient transmission of the parasites. Our experiments suggest that coronin organizes actin filaments to achieve rapid and directional motility. We also identify two signaling pathways that converge to regulate actin filament dynamics and suggest that they play a role in switching the parasite from its motility mode to a cell invasion mode.