An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes

The basic organisation of the endomembrane system is conserved in all eukaryotes and comparative genome analyses provides compelling evidence that the endomembrane system of the last common eukaryotic ancestor (LCEA) is complex with many genes required for regulated traffic being present. Although a...

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Bibliographic Details
Published in:PLoS pathogens 2013-03, Vol.9 (3), p.e1003213-e1003213
Main Authors: Kremer, Katrin, Kamin, Dirk, Rittweger, Eva, Wilkes, Jonathan, Flammer, Halley, Mahler, Sabine, Heng, Joanne, Tonkin, Christopher J, Langsley, Gordon, Hell, Stefan W, Carruthers, Vernon B, Ferguson, David J P, Meissner, Markus
Format: Article
Language:English
Subjects:
Animal diseases
Biology
Cell Line
Colleges & universities
Experiments
Fibroblasts - parasitology
Gene expression
Genetic aspects
Genomes
Guanosine triphosphatase
Humans
Microbial genetics
Organelles - metabolism
Parasites
Physiological aspects
Protein Transport
Proteins
Protozoan Proteins - genetics
Protozoan Proteins - metabolism
rab5 GTP-Binding Proteins - metabolism
Secretory Pathway
Toxoplasma
Toxoplasma - metabolism
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Summary:The basic organisation of the endomembrane system is conserved in all eukaryotes and comparative genome analyses provides compelling evidence that the endomembrane system of the last common eukaryotic ancestor (LCEA) is complex with many genes required for regulated traffic being present. Although apicomplexan parasites, causative agents of severe human and animal diseases, appear to have only a basic set of trafficking factors such as Rab-GTPases, they evolved unique secretory organelles (micronemes, rhoptries and dense granules) that are sequentially secreted during invasion of the host cell. In order to define the secretory pathway of apicomplexans, we performed an overexpression screen of Rabs in Toxoplasma gondii and identified Rab5A and Rab5C as important regulators of traffic to micronemes and rhoptries. Intriguingly, we found that not all microneme proteins traffic depends on functional Rab5A and Rab5C, indicating the existence of redundant microneme targeting pathways. Using two-colour super-resolution stimulated emission depletion (STED) we verified distinct localisations of independent microneme proteins and demonstrate that micronemal organelles are organised in distinct subsets or subcompartments. Our results suggest that apicomplexan parasites modify classical regulators of the endocytic system to carryout essential parasite-specific roles in the biogenesis of their unique secretory organelles.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003213