Abstract
Invasion of host cells by the malaria parasite involves recognition and interaction with cell-surface receptors. A wide variety of parasite surface proteins participate in this process, most of which are specific to the parasite's particular invasive form. Upon entry, the parasite has to dissociate itself from the host-cell receptors. One mechanism by which it does so is by shedding its surface ligands using specific enzymes. Rhomboid belongs to a family of serine proteases that cleave cell-surface proteins within their transmembrane domains. Here we identify and partially characterize a Plasmodium berghei rhomboid protease (PbROM1) that plays distinct roles during parasite development. PbROM1 localizes to the surface of sporozoites after salivary gland invasion. In blood stage merozoites, PbROM1 localizes to the apical end where proteins involved in invasion are also present. Our genetic analysis suggests that PbROM1 functions in the invasive stages of parasite development. Whereas wild-type P. berghei is lethal to mice, animals infected with PbROM1 null mutants clear the parasites efficiently and develop long-lasting protective immunity. The results indicate that P. berghei Rhomboid 1 plays a nonessential but important role during parasite development and identify rhomboid proteases as potential targets for disease control.
Highlights
For successful development and transmission, Plasmodium has to invade multiple cell types both in the mammalian host and in the mosquito vector
We use a genetic approach to study the function of Plasmodium berghei rhomboid 1 (PbROM1)
PbROM1 is expressed in both vertebrate and mosquito stages of parasite development, and the protein is present in secretory organelles that contain other parasite molecules required for invasion
Summary
For successful development and transmission, Plasmodium has to invade multiple cell types both in the mammalian host and in the mosquito vector. Sporozoites released from mature oocysts invade the salivary glands from where they are delivered to the vertebrate host by a mosquito bite. The parasite surface ligand-receptor complexes translocate towards the posterior end Dissociation of these interactions by proteolytic processing is thought to be important, as this enables the parasite to move forward [18,19,20]. In another Apicomplexan parasite-Toxoplasma-the TRAP homologue MIC2 is cleaved within its transmembrane domain releasing the receptorbinding domain from the parasite surface [18] and Plasmodium merozoite TRAP (MTRP) appears to be cleaved in a similar manner [16]
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