title: An essential dual-function complex mediates erythrocyte invasion and channel-mediated nutrient uptake in malaria parasites.
abstract: Malaria parasites evade immune detection by growth and replication within erythrocytes. After erythrocyte invasion, the intracellular pathogen must increase host cell uptake of nutrients from plasma. Here, we report that the parasite-encoded RhopH complex contributes to both invasion and channel-mediated nutrient uptake. Asrhoph2andrhoph3gene knockouts were not viable in the humanP. falciparumpathogen, we used conditional knockdowns to determine that the encoded proteins are essential and to identify their stage-specific functions. We exclude presumed roles for RhopH2 and CLAG3 in erythrocyte invasion but implicate a RhopH3 contribution either through ligand-receptor interactions or subsequent parasite internalization. These proteins then traffic via an export translocon to the host membrane, where they form a nutrient channel. Knockdown of either RhopH2 or RhopH3 disrupts the entire complex, interfering with organellar targeting and subsequent trafficking. Therapies targeting this complex should attack the pathogen at two critical points in its cycle.
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ito
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.
authors.forename: Marc A
authors.identifier: 0000-0001-9880-0783
authors.initials: MA
authors.lastname: Schureck
authors.affiliation: Laboratory of Malaria and Vector Research, NIAID, National Institutes of Health, Rockville, United States.
authors.forename: Sanjay A
authors.identifier: 0000-0003-2150-2483
authors.initials: SA
authors.lastname: Desai
mesh_terms: D000818:Animals; D004912:Erythrocytes / Q000469:parasitology*; D055785:Gene Knockdown Techniques; D055786:Gene Knockout Techniques; D020043:Genes, Essential; D006801:Humans; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; C065352:rhoptry associated protein, Plasmodium; C073168:rhoptry-associated antigen-2, Plasmodium
keywords: P. falciparum; cell biology; erythrocyte; human; infectious disease; malaria; merozoite invasion; microbiology; nutrient uptake; plasmodial surface anion channel