Identification of the Moving Junction Complex of Toxoplasma gondii: A Collaboration between Distinct Secretory Organelles

Abstract

Apicomplexan parasites, including Toxoplasma gondii and Plasmodium sp., are obligate intracellular protozoa. They enter into a host cell by attaching to and then creating an invagination in the host cell plasma membrane. Contact between parasite and host plasma membranes occurs in the form of a ring-shaped moving junction that begins at the anterior end of the parasite and then migrates posteriorly. The resulting invagination of host plasma membrane creates a parasitophorous vacuole that completely envelops the now intracellular parasite. At the start of this process, apical membrane antigen 1 (AMA1) is released onto the parasite surface from specialized secretory organelles called micronemes. The T. gondii version of this protein, TgAMA1, has been shown to be essential for invasion but its exact role has not previously been determined. We identify here a trio of proteins that associate with TgAMA1, at least one of which associates with TgAMA1 at the moving junction. Surprisingly, these new proteins derive not from micronemes, but from the anterior secretory organelles known as rhoptries and specifically, for at least two, from the neck portion of these club-shaped structures. Homologues for these AMA1-associated proteins are found throughout the Apicomplexa strongly suggesting that this moving junction apparatus is a conserved feature of this important class of parasites. Differences between the contributing proteins in different species may, in part, be the result of selective pressure from the different niches occupied by these parasites. Among the world's most important pathogens are a group known as the Apicomplexa. These are single-celled, eukaryotic parasites that cause a range of diseases including malaria and some AIDS opportunistic infections, such as toxoplasmosis and cryptosporidiosis. The group shares several properties: first, they are all intracellular parasites that require a host cell in which to grow; second, they all have an extraordinary collection of structures at their front end, the eponymous apical complex; and third, during invasion, each forms an intimate association with the host cell surface. This ring of contact, which migrates down the parasite as invasion proceeds, is termed the moving junction (MJ). Until now, the composition of the MJ has been a complete mystery. Here, the authors identify four proteins that apparently make up the MJ in Toxoplasma gondii and show that the structure is apparently conserved throughout the Apicomplexa, including in the malaria parasites. Surprisingly, forming the MJ appears to be a collaboration between two, completely different secretion organelles within the apical complex. Detailed study of the MJ complex will shed light on what adaptations each parasite has evolved for the hosts and the cell type they infect. It may also represent an important target for prevention and treatment.