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The Leishmania pathogenicity factors GP63 and LPG traffic in vesicular structures via a Sec22b-mediated pathway

Arango Duque, Guillermo; Jardim, Armando; Desjardins, Michel; Descoteaux, Albert . The Leishmania pathogenicity factors GP63 and LPG traffic in vesicular structures via a Sec22b-mediated pathway In: International Congress of Imunology, 21-26 August 2016, Melbourne, Australia.

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Résumé

Leishmania parasites conquer their hosts by sabotaging phagocytosis. Phagosomes become microbicidal via membrane exchanges that are mediated by soluble NSF attachment protein receptors (SNAREs), with organelles such as the ERGolgi intermediate compartment (ERGIC). Leishmania uses pathogenicity factors such as the GP63 protease and lipophosphoglycan (LPG) to cleave host proteins involved in immunity and retard phagosome maturation, respectively. How GP63 and LPG traffic from the phagosome to the cytoplasm remained unknown. We hypothesized that these molecules are redistributed in the cytoplasm of infected cells in vesicles whose trafficking is mediated by host organelles. Using confocal microscopy, we demonstrated that GP63 and LPG were found in vesicles dispersed in the cytoplasm of infected phagocytes. Flotation assays showed that GP63 and LPG localize to low-density fractions containing vesicles, and to denser fractions enriched in ER/ERGIC proteins. We observed via immunofluorescence that these markers also colocalized with GP63 and LPG. Interestingly, Brefeldin A- and Monensin-mediated disruption of ER-Golgi transport hindered the redistribution of GP63 and LPG, as well as the cleavage of Syt XI, a GP63 substrate. This prompted us to study the role of the SNARE Sec22b - which regulates ER-Golgi transport - on the redistribution of these parasitemolecules. In infected cells transduced with shRNA to Sec22b, the trafficking of GP63 and LPG was hampered. Moreover, this ensued in lessened cleavage of Syt XI. Together, our data revealed a novel mechanismby which an intracellular pathogen hijacks membrane fusion regulators in the ER/ERCIG to promote the trafficking of the pathogen’s pathogenicity factors.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: no 1180
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 23 avr. 2018 21:02
Dernière modification: 23 avr. 2018 21:11
URI: http://espace.inrs.ca/id/eprint/5929

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