**25. Reorientation and secretory organelles**

After binding to erythrocyte, the parasite reorient itself so that the 'apical end' of the parasite is juxtaposed to the erythrocyte membrane. This merozoite reorientation also coincides with a transient erythrocyte deformation. Apical membrane antigen-I (AMA-I) has been implicated in this reorientation.[58] AMA-I is a transmembrane protein localized at the apical end of the merozoite and bind erythrocytes. Antibodies against AMA-I do not interfer with the initial contact between merozoite and erythrocytes thus suggesting that AMA-I is not involved in merozoite attachment. But antibodies against AMA-I prevent the reorientation of the merozoite and thereby block merozoite invasion.

specialized secretory organelles are located at the invasive stages of apicomplexan parasites. Three morphologically distinct apical organelles are detected by electron microscopy; mocronemes, rhoptries, and dense granules. Dense granules are not always included with the apical oganelles and probably represent a heterogeneous population of secretory vesicles.

The initial interaction between the merozoite and the erythrocyte is probably a random collision and presumably involves reversible interactions between proteins on the merozoite surface and the host erythrocyte. Several merozoite surface proteins have been described. The best characterized is merozoite surface protein – 1 (MSP-1). Circumstantial evidence implicating MSP – I in erythrocyte invasion include its uniform distribution over the merozoite surface and the observation that antibodies against MSP-I inhibit invasion.[54] In addition, MSP-I does bind to band 3.[55] However, a role for MSP-I in invasion has not been definitively demonstrated. Similarly, the circumsporozite protein (CSP) probably plays a role in targeting sporozoites to hepatocytes by interacting with heparin sulfate

Another interacting aspect of MSP-I is the proteolytic processing that is coincident with merozoite maturation and invasion.[57] A primary processing occurs at the time of merozite maturation and result in the formation of several polypeptides held together in a noncovalent complex. A secondary processing occurs coincident with merozoite invasion at a site near the C-terminus. The non-covalent complex of MSP-I polypeptide fragments is shed from the merozoite surface following proteolysis and only a small C-terminal fragment is carried into the erythrocyte. This loss of the MSP-I complex may correlate with the loss of the 'fuzzy' coat during merozoite invasion. The C-terminal fragment is attached to the merozoite surface by a GPI anchor and consists of two EGF-like modules. EGF-like modules are found in a variety of protein and are usually implicated in protein-protein interactions. One possibility is that the secondary proteolytic processing functions to expose the EGF-like modules which strengthen the interactions between merozoite and erythrocyte. The

importance of MSP-I and its processing are implied from the following observations:

The exact role(s) which MSP-I and its processing play in the merozoite invasion process are

After binding to erythrocyte, the parasite reorient itself so that the 'apical end' of the parasite is juxtaposed to the erythrocyte membrane. This merozoite reorientation also coincides with a transient erythrocyte deformation. Apical membrane antigen-I (AMA-I) has been implicated in this reorientation.[58] AMA-I is a transmembrane protein localized at the apical end of the merozoite and bind erythrocytes. Antibodies against AMA-I do not interfer with the initial contact between merozoite and erythrocytes thus suggesting that AMA-I is not involved in merozoite attachment. But antibodies against AMA-I prevent the

specialized secretory organelles are located at the invasive stages of apicomplexan parasites. Three morphologically distinct apical organelles are detected by electron microscopy; mocronemes, rhoptries, and dense granules. Dense granules are not always included with the apical oganelles and probably represent a heterogeneous population of secretory

• Vaccination with the EGF-like modules can protect against malaria, and • Inhibition of the proeolytic processing blocks merozoite invasion.

reorientation of the merozoite and thereby block merozoite invasion.

**25. Reorientation and secretory organelles** 

**24. Merozoite surface proteins and host- parasite interaction** 

proteoglycans . [56]

not known.

vesicles.

The contents of the apical organelles are expelled as the parasite invades, thus suggesting that these organelles play some role in invasion. Experiments in *Toxoplasma gondii* indicate that the micronemes are expelled first and occur with initial contact between the parasite and host.[59] An increase in the cytoplasmic concentration of calcium is associated with microneme discharge.[60] as is typical of regulated secretion in other eukaryotes.

Dense granule contents are released after the parasite has completed its entry, and therefore, are usually implicated in the modification of the host cell. For RESA is localized to dense granules in merozoites and is transported to the host erythrocyte membrane shortly after merozoite invasion.[61] However, subtilisin-like proteases, which are implicated in the secondary proteolytic processing of MSP-I (discussed above), have also been localized to *Plasmodium* dense granules.[62,63] If MSP-I processing is catalyzed by these proteases, then at least some dense granules must be discharged at the time of invasion.
