During the bloodstream stage of the malaria life cycle, merozoites that are derived either from infected erythrocytes or infected hepatocytes infect erythrocytes by a well-characterized process that involves three organelles that are present in the apical part of the cell: rhoptries, micronemes and dense granules. These organelles mediate merozoite attachment, invasion and formation of the parasitophorous vacuole (PV), in which the parasite grows. Eventually, numerous daughter merozoites erupt out of the infected erythrocyte, but to escape they must breach the membranes of the PV and the cell.
PfSUB1 was identified by Blackman and colleagues in 1998 as one of three subtilisin-like serine proteases that are present in P. falciparum. Here, Yeoh et al. sought to probe the role of PfSUB1 in the biology of malaria. Unsuccessful attempts to disrupt the pfsub1 gene proved that it is essential. By tagging the carboxyl terminus of PfSUB1 with a triple haemagglutinin (HA) tag to yield PfSUB1HA3, they were able to scrutinize the subcellular localization of PfSUB1. In accordance with their previous observations, PfSUB1 was localized to the apical part of the cell, but was absent from rhoptries and micronemes. Using antibodies to ring-infected erythrocyte surface antigen (RESA), a marker protein for dense granules, and antibodies to either the HA tag or the PfSUB1 protein, they showed that PfSUB1 is present in a subset of dense granules with an altered morphology that they named exonemes. Further studies showed that although RESA was released in newly infected erythrocytes, PfSUB1 was only found in the supernatants of ruptured maturing merozoites (schizonts). This led the authors to propose that PfSUB1 was involved in a pre-invasion event, such as merozoite egress.
This is a preview of subscription content, access via your institution
