Erythrocyte-binding activity of Plasmodium yoelii apical membrane antigen-1 expressed on the surface of transfected COS-7 cells

Malaria merozoite surface and apical organellar molecules facilitate invasi on into the host erythrocyte. The underlying molecular mechanisms of invasi on are poorly understood, and there are few data to delineate roles for ind ividual merozoite proteins. Apical membrane antigen-1 (AMA-1) is a conserve d apicomplexan protein present in the apical organelle complex and at times on the surface of Plasmodium and Toxoplasma zoites. AMA-1 domains 1/2 are conserved between Plasmodium and Toxoplasma and have similarity to the defi ned ligand domains of MAEBL, an erythrocyte-binding protein identified from Plasmodium yoelii. We expressed selected portions of the AMA-1 extracellul ar domain on the surface of COS-7 cells to assay for erythrocyte-binding ac tivity. The P. yoelii AMA-1 domains 1/2 mediated adhesion to mouse and rat erythrocytes, but not to human erythrocytes. Adhesion to rodent erythrocyte s was sensitive to trypsin and chymotrypsin, but not to neuraminidase. Othe r parts of the AMA-I ectodomain, including the full-length extracellular do main, mediated significantly less erythrocyte adhesion activity than the co ntiguous domains 1/2. The results support the role of AMA-1 as an adhesion molecule during merozoite invasion of erythrocytes and identify highly cons erved domains 1/2 as the principal ligand of the Plasmodium AMA-1 and possi bly the Toxoplasma AMA-1. Identification of the AMA-1 ligand domains involv ed in interaction between the parasite and host cell should help target the development of new therapies to block growth of the blood-stage malaria pa rasites. (C) 2001 Elsevier Science B.V. All rights reserved.