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      Secretory traffic in the eukaryotic parasite Toxoplasma gondii : less is more

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          Abstract

          Name a single-celled eukaryote that boasts a small genome size, is easily cultivated in haploid form, for which a wide variety of molecular genetic tools are available, and that exhibits a simple, polarized secretory apparatus with a well-defined endoplasmic reticulum and Golgi that can serve as a model for understanding secretion. Got it? Now name a cell with all these attributes that contains at least a dozen distinct and morphologically well-defined intracellular organelles, including three distinct types of secretory vesicles and two endosymbiotic organelles. Not so sure anymore?

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          Most cited references56

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          RADIOAUTOGRAPHIC STUDIES OF CHOLINE INCORPORATION INTO PERIPHERAL NERVE MYELIN

          This radioautographic study was designed to localize the cytological sites involved in the incorporation of a lipid precursor into the myelin and the myelin-related cell of the peripheral nervous system. Both myelinating and fully myelinated cultures of rat dorsal root ganglia were exposed to a 30-min pulse of tritiated choline and either fixed immediately or allowed 6 or 48 hr of chase incubation before fixation. After Epon embedding, light and electron microscopic radioautograms were prepared with Ilford L-4 emulsion. Analysis of the pattern of choline incorporation into myelinating cultures indicated that radioactivity appeared all along the length of the internode, without there being a preferential site of initial incorporation. Light microscopic radioautograms of cultures at varying states of maturity were compared in order to determine the relative degree of myelin labeling. This analysis indicated that the myelin-Schwann cell unit in the fully myelinated cultures incorporated choline as actively as did this unit in the myelinating cultures. Because of technical difficulties, it was not possible to determine the precise localization of the incorporated radioactivity within the compact myelin. These data are related to recent biochemical studies indicating that the mature myelin of the central nervous system does incorporate a significant amount of lipid precursor under the appropriate experimental conditions. These observations support the concept that a significant amount of myelin-related metabolic activity occurs in mature tissue; this activity is considered part of an essential and continuous process of myelin maintenance and repair.
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            Toxoplasmic encephalitis in AIDS.

            Involvement of the central nervous system (CNS) is common in patients with advanced disease due to human immunodeficiency virus (HIV). Symptoms range from lethargy and apathy to coma, incoordination and ataxia to hemiparesis, loss of memory to severe dementia, and focal to major motor seizures. Involvement may be closely associated with HIV infection per se, as in the AIDS dementia complex, but is frequently caused by opportunistic pathogens such as Toxoplasma gondii and Cryptococcus neoformans or malignancies such as primary lymphoma of the CNS. The clinical presentations of attendant and direct CNS involvement are remarkably non-specific and overlapping, yet a correct diagnosis is critical to successful intervention. Toxoplasmic encephalitis is one of the most common and most treatable causes of AIDS-associated pathology of the CNS. A great deal has been learned in the last 10 years about its unique presentation in the HIV-infected patient with advanced disease. Drs. Benjamin J. Luft of the State University of New York at Stony Brook and Jack S. Remington of the Stanford University School of Medicine and Palo Alto Medical Foundation's Research Institute have studied T. gondii for many years and are two of the leading experts in the field. This commentary comprises an update of their initial review (J Infect Dis 1988;157:1-6) and a presentation of the current approaches to diagnosing and managing toxoplasmic encephalitis in HIV-infected patients.
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              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.
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                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                13 May 2002
                : 157
                : 4
                : 557-563
                Affiliations
                [1 ]Section of Infectious Diseases, Yale University School of Medicine, New Haven, CT 06520
                [2 ]Department of Biology, University of Pennsylvania, Philadelphia, PA 19104
                Author notes

                Address correspondence to Keith Joiner, Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, 333 Cedar St., New Haven, CT 06520-8022. Tel.: (203) 785-2115. Fax: (203) 785-3864. E-mail: keith.joiner@ 123456yale.edu

                Article
                0112144
                10.1083/jcb.200112144
                2173860
                12011107
                47aabbfd-b75d-496c-9f5e-daa72aba98b7
                Copyright © 2002, The Rockefeller University Press
                History
                : 28 December 2001
                : 15 February 2002
                : 28 March 2002
                Categories
                Mini-Reviews

                Cell biology
                secretory pathway; vesicular trafficking; protozoan cell biology; apicomplexan parasites; eukaryotic evolution

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