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SNARE importance in Leishmania communal and individual PV formation

Séguin, Olivier; Descoteaux, Albert . SNARE importance in Leishmania communal and individual PV formation In: 16e symposium annuel de parasitologie moléculaire du Québec, 6-7 juin 2016, Université McGill, Montréal, QC.

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Résumé

Leishmania is the parasite responsable for leishmaniasis, a disease endemic in roughly 98 countries around the world. This disease can be visceral, cutaneous or mucocutaneous depending on the Leishmania species involved. To survive into host macrophages, Leishmania creates parasitophorous vacuoles (PV). These PVs can be either individual, small and tight around the parasite for species such as L. major or communal and spacious for species such as L. amazonensis. We propose that Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptors (SNAREs) play a central role in the formation of large communal PVs by providing membrane from various organelles. We first looked at the different membrane compartments directly involved in the phagosome maturation process. The SNAREs SNAP23 (plasmic membrane), VAMP3 (early endosome) and the lysosomal associated membrane protein 1 (LAMP1) were found to be recruited to the communal vacuoles while only VAMP 8 (late endosome) was accumulated to individual vacuoles. These recruitment patterns suggest that the Leishmania communal species undergo and survive a complete phagosome maturation process while conserving membrane and augmenting the PV size to dilute microbicidal molecules produced by macrophages, while the individual species blocks the maturation process to the late endosome stage. We also found that the trans-Golgi (Vti1a) and the endoplasmic reticulum (Stx18) were recruited to communal vacuoles suggesting that L. amazonensis can hijack other membrane sources. We also used VAMP3 KO macrophages to study the role of VAMP3 in communal PV formation. Within these cells we noted an increased growth of L. amazonensis and a larger vacuole size while the individual specie was left unaffected. We also noted higher level of recruitment for LC3, an autophagy marker, to the communal PV. VAMP3 KO cells have a deregulation of autophagy leading to an augmentation of LC3 that could possibly be leading to the hijacking of the autophagy system and to the augmentation of the PV size.

Type de document: Document issu d'une conférence ou d'un atelier
Mots-clés libres: -
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 01 mai 2018 20:07
Dernière modification: 01 mai 2018 20:07
URI: http://espace.inrs.ca/id/eprint/7063

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