Toxoplasma and related apicomplexan parasites are obligate intracellular pathogens that actively invade their host cells, creating a specialized vacuole within which the parasite is able to replicate. Invasion involves the establishment of a tight-junction interface between host and parasite membranes called the moving junction (MJ) through which the parasite actively penetrates the host. At the onset of invasion, a protein complex composed of RONs 2/4/5/8 is injected from specialized parasite secretory organelles called rhoptries into the host membrane. Following secretion, this RON complex localizes to the MJ throughout the invasion event and is thought to be the basis for this tight-junction. In this study, we utilize a conditional knockdown of RON5 to show that this MJ component, present at the cytosolic face of the host membrane during penetration, is crucial for invasion and for MJ complex organization. In particular, loss of RON5 results in degradation of RON2 and mistargeting of RON4 in the parasite, effectively ablating the MJ complex. We exploit this knockdown strain to evaluate RON5 processing and identify regions of the protein that are necessary for organizing the complex. Our findings demonstrate the key role of RON5 in facilitating apicomplexan host invasion and disease.
Vyšlo v časopise: RON5 Is Critical for Organization and Function of the Moving Junction Complex. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004025 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004025
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