Plasmodium falciparum: Two antigens of similar size are located in different compartments of the rhoptry

Plasmodium falciparumapical membrane antigen 1 (PfAMA-1) is translocated within micronemes along subpellicular microtubules during merozoite development

“…The peripheral labelling suggests that PfAMA-1 is located close to, or inserted into the microneme membrane. Such a location is supported by evidence from Triton-X114 extraction experiments (Peterson et al, 1989;Crewther et al, 1990) in which both the unprocessed 83 kDa and processed 66 kDa forms of PfAMA-1 partitioned into the detergent fraction, as expected of membrane proteins. When micronemes secrete their contents, their membranes must fuse either directly with the merozoite plasma membrane or indirectly via the rhoptry ducts, so that a micronemal transmembrane protein could relocate on to the merozoite surface simply by diffusion along membranes.…”

“…whole ectodomain of PfAMA-1 indicates clearly that this molecule is micronemal and, at least within the schizont, not a rhoptry protein, supporting the recent findings of a micronemal location by Healer et al (Healer et al, 2002) based on FI and IEM with a monoclonal antibody recognizing only the unprocessed (83 kDa) form of PfAMA-1. Healer et al proposed that, because their antibody did not detect the apical rhoptry labelling reported by Crewther et al (Crewther et al, 1990), the rhoptry tips must contain only the 66 kDa molecule. Our antibodies detect both the 83 kDa and 66 kDa forms of PfAMA-1 in micronemes but we still failed to find evidence of rhoptry labelling at any time within the schizont.…”

“…It is synthesised as an 83 kDa molecule and processed within the schizont by the loss of its N-terminal pro-domain to 66 kDa, and then relocates on to the merozoite surface; PfAMA-1 is further cleaved in the free merozoite prior to or at invasion (Howell et al, 2001). Within merozoites, PfAMA-1 has been localized by IEM to the apical ends of rhoptries, with indications of a micronemal involvement (Crewther et al, 1990). However, there have been doubts about its rhoptry assignment because, unlike typical rhoptry proteins, PfAMA-1 is synthesized very late in merozoite development involvement (Crewther et al, 1990) and its Toxoplasma gondii homologue (TgAMA-1) is now known to be micronemal (Donahue et al, 2000;Hehl et al, 2000).…”

“…Within merozoites, PfAMA-1 has been localized by IEM to the apical ends of rhoptries, with indications of a micronemal involvement (Crewther et al, 1990). However, there have been doubts about its rhoptry assignment because, unlike typical rhoptry proteins, PfAMA-1 is synthesized very late in merozoite development involvement (Crewther et al, 1990) and its Toxoplasma gondii homologue (TgAMA-1) is now known to be micronemal (Donahue et al, 2000;Hehl et al, 2000). Immediately before submission of this work, Healer et al (Healer et al, 2002) published an IEM study showing that a monoclonal antibody to the full length (unprocessed) 83 kDa, but not the processed 66 kDa, form of PfAMA-1 (therefore presumably recognizing the pro-domain) labels micronemes rather than rhoptries.…”

Longitudinal study of natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in a holoendemic region of malaria in western Kenya: Asembo Bay Cohort Project VIII.

“…1 The 83-kDa AMA-1 protein of Plasmodium falciparum and its Plasmodium knowlesi analog (a 66-kDa protein) are found in the apical complex of schizonts and are transferred to the merozoite surface at the time of schizont rupture. [2][3][4] The monoclonal antibodies against this protein inhibit the invasion of P. knowlesi merozoites into erythrocytes, demonstrating that AMA-1 may be involved in merozoite invasion. 5,6 The gene encoding this protein has been cloned from P. falciparum.…”