Cathepsin L occupies a vacuolar compartment and is a protein maturase within the endo/exocytic system of Toxoplasma gondii

Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA.
Molecular Microbiology (Impact Factor: 4.42). 04/2010; 76(6):1340-57. DOI: 10.1111/j.1365-2958.2010.07181.x
Source: PubMed


Regulated exocytosis allows the timely delivery of proteins and other macromolecules precisely when they are needed to fulfil their functions. The intracellular parasite Toxoplasma gondii has one of the most extensive regulated exocytic systems among all unicellular organisms, yet the basis of protein trafficking and proteolytic modification in this system is poorly understood. We demonstrate that a parasite cathepsin protease, TgCPL, occupies a newly recognized vacuolar compartment (VAC) that undergoes dynamic fragmentation during T. gondii replication. We also provide evidence that within the VAC or late endosome this protease mediates the proteolytic maturation of proproteins targeted to micronemes, regulated secretory organelles that deliver adhesive proteins to the parasite surface during cell invasion. Our findings suggest that processing of microneme precursors occurs within intermediate endocytic compartments within the exocytic system, indicating an extensive convergence of the endocytic and exocytic pathways in this human parasite.

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    • "Recent studies in T. gondii have deciphered some of the machinery involved in trafficking to apical organelles (reviewed in [5]). Early studies noted the existence of an intermediate compartment in the trafficking of micronemal proteins [6], which was subsequently shown to be an endosome-like compartment for the removal of microneme propeptides [7]. Rhoptry and microneme biogenesis in T. gondii occur from the fusion of post-Golgi vesicles, whose scission is likely regulated by a dynamin related protein (DrpB). "
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    • "We used overexpression under the strong tubulin promoter to detect the remaining proteins (Fig. 4C and D; Supplementary Fig. S3B and C). Interestingly , TgFYVE1, TgPX1, TgPX2 and TgPX3 were found associated with the recently described vacuolar compartment (VAC), a highly dynamic compartment that houses lysosomal markers such as cathepsin-like cysteine protease (TgCPL) (Fig. 4C) (Parussini et al., 2010). TgPX3 protein partially localized to the VAC compartment but was also detected associated with other unknown subcellular structures (Fig. 4C). "
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    Full-text · Article · Oct 2014 · Cellular Microbiology
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    • "The T. gondii VAC contains classically degradative lysosomal-like proteases, such as cathepsins involved in the maturation of MICs (TgMIC2 and TgM2AP). These findings suggest that processing of microneme precursors occurs in intermediate endocytic compartments within the exocytic system, indicating an extensive convergence of the endocytic and exocytic pathways in T. gondii (Parussini et al., 2010). Light microscopy revealed another novel organelle in T. gondii with similarity to the vacuole in plant cells (Miranda et al., 2010; Francia et al., 2011). "
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