**29. Summary**

Merozoite invasion is a complex and ordered process. A tentative model of merozoite invasion includes:


Biology of Malaria Parasites 29

The extracellular domain is characterized by 1-5 copies of Duffy-binding (DBL) domains. These DBL domains are similar to the receptor-binding region of the ligand involved in merozoite invasion (discussed above). The DBL domain exhibit a conserved spacing of cystrine and hydrophobic residues, but otherwise show little homology analysis indicates that there are five distinct classes (designated as α,β,γ,δ………… and…ε…..) of DBL domains.[83] The first DBL is always the same type (designated α) and this is followed by a cysteine- rich interdomain region (CIDR). A variable number of DBL in various orders make

Several possible endothelial receptors have been identified by testing the ability of infected erythrocytes to bind in static adherence assays.[84] One of the best characterized among these is CD36, an 88 kDa intergral membrane protein found on monocytes, platelets and endothelial cells infected erythrocytes from most parasite isolates bind to CD36 and the binding domain has been mapped to the CIDR of *Pf*EMPI. However, CD36 has not been detected on endothelial cells of the cerebral blood vessels and parasites from clinical isolates tend to adhere to both CD36 and intracellular adhesion molecule – 1 (ICAMI). ICAMI is a member of the immunoglobulin superfamily and functions in cell-cell adhesion. In addition, sequestration of infected erythrocytes and ICAMI expression has been co-localized in the

Chondroitin sulfate A (CSA) has been implicated in the cytoadhernce within the placenta and may contribute to the adverse effects of *P. falciparum* during pregnancy. The role of some the other potential receptors is not clear. For example, adherence to thrombospondin exhibits a low affinity and cannot support binding under flow condition. Binding to VCAMI, PECAMI and E- selectin appear to be rare and questions about their constrictive expression on endothelial cells have been raised. However, cytoadherence could involve

Resetting is another adhesive phenomenon exhibited by *P. falciparum*-infected erythrocytes. Infected erythrocytes from some parasite isolates will bind multiple uninfected erythrocytes and *Pf*EMPI appears to have a role in at least some resetting. Possible receptors include complement receptor-I (CRI), blood group A antigen, or glycosaminoglycan moieties on an

up the rest of the extracellular domain of *Pf*EMP-I.

• **CD36** 

• CR-I

brain.[85]

• Ig Superfamily • **ICAMI**  • VCAMI • PECAMI

• Heparin sulfate • Hyaluronic acid • E- selectin • Thrombospondin • **Resetting Ligands** 

• Blood group A Ag • Glycosaminoglycan

multiple receptor/ligand interactions.

unidentified proteoglycan.

• **Chondroitin sulfate A** 

**Possible Receptors Identified By in Vitro Binding Assays** 

Many proteins that are involved in the invasion process have been identified. However, much still remains to be learned about the cellular and molecular biology of merozoite invasion.[73,74]
