A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites.

Abstract

Plasmodium sporozoites are transmitted through the bite of infected mosquitoes and invade hepatocytes as a first and obligatory step of the parasite life cycle in man. Hepatocyte invasion involves proteins secreted from parasite vesicles called micronemes, the most characterized being the thrombospondin-related adhesive protein (TRAP). Here we investigated the expression and function of another microneme protein recently identified in Plasmodium falciparum sporozoites, apical membrane antigen 1 (AMA-1). P. falciparum AMA-1 is expressed in sporozoites and is lost after invasion of hepatocytes, and anti-AMA-1 antibodies inhibit sporozoite invasion, suggesting that the protein is involved during invasion of hepatocytes. As observed with TRAP, AMA-1 is initially mostly sequestered within the sporozoite. Upon microneme exocytosis, AMA-1 and TRAP relocate to the sporozoite surface, where they are proteolytically cleaved, resulting in the shedding of soluble fragments. A subset of serine protease inhibitors blocks the processing and shedding of both AMA-1 and TRAP and inhibits sporozoite infectivity, suggesting that interfering with sporozoite proteolytic processing may constitute a valuable strategy to prevent hepatocyte infection.

• Authors: Olivier Silvie, Jean-François Franetich, Stéphanie Charrin, Markus S Mueller, Anthony Siau, Myriam Bodescot, Eric Rubinstein, Laurent Hannoun, Yupin Charoenvit, Clemens H Kocken, Alan W Thomas, Geert-Jan Van Gemert, Robert W Sauerwein, Michael J Blackman, Robin F Anders, Gerd Pluschke, Dominique Mazier
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 279 Issue 10 Pg. 9490-6 (Mar 05 2004) ISSN: 0021-9258 [Print] United States
• PMID: 14676185 (Publication Type: Journal Article)

Chemical References

• Antigens, Protozoan
• Membrane Proteins
• Protozoan Proteins
• apical membrane antigen I, Plasmodium
• thrombospondin-related adhesive protein, protozoan

Topics

• Animals
• Antigens, Protozoan (metabolism)
• Cells, Cultured
• Hepatocytes (metabolism, parasitology)
• Humans
• Membrane Proteins (metabolism)
• Plasmodium falciparum (metabolism, pathogenicity)
• Protozoan Proteins (metabolism)
• Sporozoites (metabolism, pathogenicity)