Abstract
Profilin is an actin monomer binding protein that provides ATP-actin for incorporation into actin filaments. In contrast to higher eukaryotic cells with their large filamentous actin structures, apicomplexan parasites typically contain only short and highly dynamic microfilaments. In apicomplexans, profilin appears to be the main monomer-sequestering protein. Compared to classical profilins, apicomplexan profilins contain an additional arm-like β-hairpin motif, which we show here to be critically involved in actin binding. Through comparative analysis using two profilin mutants, we reveal this motif to be implicated in gliding motility of Plasmodium berghei sporozoites, the rapidly migrating forms of a rodent malaria parasite transmitted by mosquitoes. Force measurements on migrating sporozoites and molecular dynamics simulations indicate that the interaction between actin and profilin fine-tunes gliding motility. Our data suggest that evolutionary pressure to achieve efficient high-speed gliding has resulted in a unique profilin-actin interface in these parasites.
Highlights
Motility of adherent cells is important for both uni- and multicellular organisms
Profilin localization is consistent with the localization of GFP-actin, which was found in the cytosol and the nucleus [43]
We found no difference between the wild-type P. berghei and the line expressing wild type P. falciparum profilin (Fig 6C and 6D)
Summary
Motility of adherent cells is important for both uni- and multicellular organisms. In higher eukaryotic cells, motility plays a key role in, for example embryo- and organogenesis [1], immune responses [2], and cancer metastasis [3]. The active substrate-dependent gliding motility of these parasites is essential for them to enter red blood cells, to pass through the epithelium of the mosquito midgut, and for transmission from the mosquito to the vertebrate host [5]. In the Plasmodium spp. infecting mammals, the sporozoites first migrate rapidly within the dermis and subsequently enter either the blood or the lymph vessels [13]. Those entering the blood stream adhere to the liver endothelium and actively penetrate the liver parenchyma to infect hepatocytes [14]
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