Domain III of Plasmodium falciparum apical membrane antigen 1 binds to the erythrocyte membrane protein Kx

Kentaro Kato, D. C.Ghislaine Mayer, Sanjay Singh, Marion Reid, Louis H. Miller

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Plasmodium falciparum apical membrane antigen 1 (AMA1) is located in the merozoite micronemes, an organelle that contains receptors for invasion, suggesting that AMA1 may play a role in this process. However, direct evidence that P. falciparum AMA1 binds to human erythrocytes is lacking. In this study, we determined that domain III of AMA1 binds to the erythrocyte membrane protein, Kx, and that the rate of invasion of Kxnull erythrocytes is reduced, indicating a significant but not unique role of AMA1 and Kx in parasite invasion of erythrocytes. Domains I/II/III, domains I/II and domain III of AMA1 were expressed on the surface of CHO-K1 cells, and their ability to bind erythrocytes was determined. We observed that each of these domains failed to bind untreated human erythrocytes. In contrast, domain III, but not the other domains of AMA1, bound to trypsin-treated human erythrocytes. We tested the binding of AMA1 to trypsin-treated genetically mutant human erythrocytes, missing various erythrocyte membrane proteins. AMA1 failed to bind trypsin-treated Kxnull (McLeod) erythrocytes, which lack the Kx protein. Furthermore, treatment of human erythrocytes with trypsin, followed by α-chymotrypsin, cleaved Kx and destroyed the binding of AMA1 to human erythrocytes. Lastly, the rate of invasion of Kx null erythrocytes by P. falciparum was significantly lower than Kx-expressing erythrocytes. Taken together, our data suggest that AMA1 plays an important, but not exclusive, role in invasion of human erythrocytes through a process that involves exposure or modification of the erythrocyte surface protein, Kx, by a trypsin-like enzyme.

Original languageEnglish
Pages (from-to)5552-5557
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number15
DOIs
Publication statusPublished - 2005 Apr 12
Externally publishedYes

Keywords

  • Erythrocyte recognition
  • Invasion
  • Malaria
  • McLeod
  • Merozoite

ASJC Scopus subject areas

  • General

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