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The exocytosis regulator Synaptotagmin V controls phagocytosis in macrophages

Vinet, Adrien F.; Fukuda, Mitsunori; Descoteaux, Albert . The exocytosis regulator Synaptotagmin V controls phagocytosis in macrophages In: 8e symposium annuel de parasitologie moléculaire du Québec, 12-13 juin 2008, UQAM.

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Résumé

Phagocytosis is initiated through binding of a particle by receptors that trigger actin polymerization at the site of contact. Previous studies showed a focalized exocytosis of membrane from internal vesicles at the phagocytic cup. Components of SNAREs are essential for this process. Synaptotagmins (Syt) are a large family of membrane proteins that contains two Ca2+-C2 domains which can bind phospholipids as well as SNARE components. Although they were identified and widely studied in neuronal cells for their role in the regulation of neurotransmitters exocytosis, few studies have demonstrated the expression of synaptotagmin isoforms in macrophages. Several signaling molecules, including members of the protein kinase C (PKC) superfamily participate in the regulation of actin polymerisation and phagolysosome biogenesis. Using a proteomic approach, we identified Syt V as a new potential partner to PKC-a in regulating phagocytosis. We showed that Syt V is expressed in macrophages and that a large part is localized on recycling endosomes. Moreover, we observed the recruitment of Syt V to phagosomes containing various particles of wich Leishmania donovani indicating that Syt V is recruited independently of the phagocytic receptors involved. We also demonstrated an early recruitment of Syt V in macrophages and an accumulation throughout the maturation process notably for both promastigote and amastigote forms of Leishmania donovani. Silencing of Syt V by RNAi revealed a key role for this protein in the regulation of phagocytosis. Collectively, these results showed for the first time the importance of Syt V in the regulation of an important innate function of macrophages and suggest that Syt V acts as a positive modulator of exocytosis with a key role in the regulation of focal exocytosis during phagocytosis.

Type de document: Document issu d'une conférence ou d'un atelier
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 02 mai 2018 19:56
Dernière modification: 02 mai 2018 19:56
URI: http://espace.inrs.ca/id/eprint/7100

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