RAP1 controls rhoptry targeting of RAP2 in the malaria parasite Plasmodiumfalciparum

Rhoptry associated protein 1 (RAP1) and 2 (RAP2), together with a poorly de scribed third protein RAP3, form the low molecular weight complex within th e rhoptries of Plasmodium falciparum. These proteins are thought to play a role in erythrocyte invasion by the extracellular merozoite and are importa nt vaccine candidates. We used gene-targeting technology in P. falciparum b lood-stage parasites to disrupt the RAP1 gene, producing parasites that exp ress severely truncated forms of RAP1. Immunoprecipitation experiments sugg est that truncated RAP1 species did not complex with RAP2 and RAP3. Consist ent with this were the distinct subcellular localizations of RAP1 and 2 in disrupted RAP1 parasites, where RAP2 does not traffic to the rhoptries but is instead located in a compartment that appears related to the lumen of th e endoplasmic reticulum, These results suggest that RAP1 is required to loc alize RAP2 to the rhoptries, supporting the hypo-thesis that rhoptry biogen esis is dependent in part on the secretory pathway in the parasite. The obs ervation that apparently host-protective merozoite antigens are not essenti al for efficient erythrocyte invasion has important implications for vaccin e design.