62
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

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

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Synopsis

          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.

          Related collections

          Most cited references55

          • Record: found
          • Abstract: found
          • Article: not found

          Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite.

          Toxoplasma gondii is an obligate intracellular parasite that invades a wide range of vertebrate host cells. We demonstrate that invasion is critically dependent on actin filaments in the parasite, but not the host cell. Invasion into cytochalasin D (CD)-resistant host cells was blocked by CD, while parasite mutants invaded wild-type host cells in the presence of drug. CD resistance in Toxoplasma was mediated by a point mutation in the single-copy actin gene ACT1. Transfection of the mutant act1 allele into wild-type Toxoplasma conferred motility and invasion in the presence of CD. We conclude that host cell invasion by Toxoplasma, and likely by related Apicomplexans, is actively powered by an actin-based contractile system in the parasite.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts.

            Invasion of vertebrate cells by the protozoan Toxoplasma gondii is accompanied by regulated protein secretion from three distinct parasite organelles called micronemes, rhoptries, and dense granules. We have compared the kinetics of secretion from these different compartments during host cell invasion using immunofluorescence, immunoelectron microscopy, and quantitative immunoassays. Binding to the host cell triggered apical release of the micronemal protein MIC2 at the tight attachment zone that forms between the parasite and the host cell. In a second step, invagination of the host cell plasma membrane was initiated by discharge of the rhoptry protein ROP1 to form a nascent parasitophorous vacuole (PV). ROP1 was fully discharged into the vacuole by the time invasion was complete. In contrast to these very rapid early events, release of the dense granule markers GRA1 and NTPase was delayed until after the parasite was fully within the PV, eventually peaking at 20 min post-invasion. The sequential triggering of secretion from different organelles implies that their release is governed by separate signals and that their contents mediate distinct phases of intracellular parasitism.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite

              Invasion of erythrocytes by merozoites of the monkey malaria, Plasmodium knowlesi, was investigated by electron microscopy. The apical end of the merozoite makes initial contact with the erythrocyte, creating a small depression in the erythrocyte membrane. The area of the erythrocyte membrane to which the merozoite is attached becomes thickened and forms a junction with the plasma membrane of the merozoite. As the merozoite enters the invagination in the erythrocyte surface, the junction, which is in the form of a circumferential zone of attachment between the erythrocyte and merozoite, moves along the confronted membranes to maintain its position at the orifice of the invagination. When entry is completed, the orifice closes behind the parasite in the fashion of an iris diaphragm, and the junction becomes a part of the parasitophorous vacuole. The movement of the junction during invasion is an important component of the mechanism by which the merozoite enters the erythrocyte. The extracellular merozoite is covered with a prominent surface coat. During invasion, this coat appears to be absent from the portion of the merozoite within the erythrocyte invagination, but the density of the surface coat outside the invagination (beyond the junction) is unaltered.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS Pathog
                ppat
                PLoS Pathogens
                Public Library of Science (San Francisco, USA )
                1553-7366
                1553-7374
                October 2005
                21 October 2005
                : 1
                : 2
                : e17
                Affiliations
                [1 ] Department of Microbiology and Immunology, Stanford University, Stanford, California, United States of America
                [2 ] Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, United States of America
                [3 ] Department of Microbiology and Immunology, University of California, Los Angeles, Los Angeles, California, United States of America
                Northwestern University Medical School, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: jboothr@ 123456stanford.edu
                Article
                05-PLPA-RA-0098R2 plpa-01-02-04
                10.1371/journal.ppat.0010017
                1262624
                16244709
                6cf2e777-b9e0-473d-aa82-d505f63faf98
                Copyright: © 2005 Alexander et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 14 July 2005
                : 12 September 2005
                Categories
                Research Article
                Cell Biology
                Parasitology
                Eukaryotes
                None
                Custom metadata
                Alexander DL, Mital J, Ward GE, Bradley P, Boothroyd JC (2005) Identification of the moving junction complex of Toxoplasma gondii: A collaboration between distinct secretory organelles. PLoS Pathog 1(2): e17.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

                Comments

                Comment on this article