No Slide Title Cell Biology of Plasmodium Mark F Wiser http //www tulane edu/~wiser/malaria/ • Merozoite invasion involves specific interactions with the host erythrocyte • The actively growing parasi[.]
Cell Biology of Plasmodium Mark F Wiser http://www.tulane.edu/~wiser/malaria/ • Merozoite invasion involves specific interactions with the host erythrocyte • The actively growing parasite places metabolic and other demands on the host cell • Ultrastructural modifications are evident in the infected erythrocyte Plasmodium Invasive Stages ookinete (motile) • mosquito gut epithelial cells sporozoite (motile) • mosquito salivary glands • hepatocytes merozoite (non-motile) • erythrocytes Bannister et al (2003) J Cell Sci 116, 3825 Steps in Merozoite Invasion Reorientation • accompanied by erythrocyte deformation • AMA-1 implicated* • apical membrane antigen-1 • binds erythrocytes • antibodies inhibit invasion and reorientation • antibodies not inhibit initial attachment *Mitchell et al (2004) Inf Imm 72, 154 Secretory (Apical) Organelles Organelle Shape Rhoptry Microneme Dense Granule Teardrop Ellipsoidal Spherical Size (nm) 300 x 600 40 x 100 120 - 140 Proteins Localized to Micronemes • Merozoite proteins: • EBA-175 (sialic binding protein of P falciparum) • Duffy-binding protein (P vivax and P knowlesi) • TRAP family*: • SSP2 (sporozoite surface protein-2) ≡ TRAP (thrombospondin-related adhesive protein) • Toxoplasma, Eimeria and Cryptosporidium proteins with homology to SSP2/TRAP • CTRP, circumsporozoite- and TRAP-related protein (Plasmodium ookinete stage) *Thrombospondin family characterized by von Willebrand factor type A domain Functions in cell-cell and cell-matrix interactions Invasion Receptors/Ligands Species P falciparum P vivax, P knowlesi Host Receptor Merozoite Ligand glycophorins (sialic acid) EBA-175 Duffy Ag DBP • microneme secretion • receptor-ligand interactions • junction formation Electron micrograph from Aikawa et al (1978) J Cell Biol 77:72 • Merozoite invasion involves specific interactions with the host erythrocyte • The actively growing parasite places metabolic and other demands on the host cell • Ultrastructural modifications are evident in the infected erythrocyte Permeability to metabolites is increased in the infected erythrocyte