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

Date Published: July 13, 2016

Publisher: Public Library of Science

Author(s): Kartik S. Bane, Simone Lepper, Jessica Kehrer, Julia M. Sattler, Mirko Singer, Miriam Reinig, Dennis Klug, Kirsten Heiss, Jake Baum, Ann-Kristin Mueller, Friedrich Frischknecht, Rita Tewari.


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.

Partial Text

Malaria-causing parasites need to actively migrate at several steps in their complex life cycle [1]. Without motility they would fail, for example, to enter red blood cells or to penetrate the mosquito midgut. The stage with the most formidable motility is the sporozoite, which migrates at average speeds exceeding 1 μm/s through the skin [2,3]. Plasmodium sporozoites are formed in parasitic oocysts at the midgut wall of Anopheles mosquitoes and, after successful transmission from the mosquito to the mammalian host, ultimately differentiate in hepatocytes to generate red blood cell infecting merozoites. Sporozoites first need to emerge from the oocysts, float through the circulatory fluid of the insect, attach to and actively invade the salivary glands [1]. After ejection with the saliva during the mosquito bite, sporozoites are deposited into the dermis, where they migrate actively at high speed to attach to and enter into blood vessels [1,4]. Taken away with the blood stream they again attach to the liver endothelium and pass through this barrier to finally enter hepatocytes [4,5]. Sporozoites are crescent shaped chiral cells that can also move on diverse substrates without changing their shape at average speeds of 1–2 μm/s [6–8]. The motor driving this gliding motility is located underneath the plasma membrane in a narrow space delimited by a membrane organelle called the inner membrane complex (IMC) that subtends the plasma membrane at a distance of approximately 30 nm. Within this space, it is thought that myosin, anchored in the IMC, drives actin filaments rearwards in what resembles retrograde flow [9,10]. Actin filaments themselves are likely linked to transmembrane proteins that contain adhesive domains including an integrin-like A-domain [9,10]. This linkage thus drives parasite motility upon attachment to a substrate although it is not clear how the different transmembrane proteins transmit force [11–13]. Actin filaments are extremely short in Plasmodium as well as in related parasites and cannot be routinely visualized [14–16]. This is at least partly due to a number of differences in the actin monomer structure that prevent the formation of long filaments [17–19]. In addition, actin-binding proteins might play a role in regulating actin filament dynamics. For example, the deletion of actin depolymerizing factor in the related parasite Toxoplasma gondii leads to formation of long filaments and stalls motility [15,20]. The Plasmodium genome only encodes a small set of canonical actin-binding proteins [21–23]. The only bona-fide actin filament-binding protein in the Plasmodium genome is coronin, which shares only 31% sequence identity to Dictyostelium coronin [24]. Coronin is conserved among the different species of Plasmodium and shows 57% identity between the major human malaria-causing parasite P. falciparum and the rodent model parasite P. berghei (S1 Fig).




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