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Role of the Protein SHP-1 in the Biogenesis of the Phagolysosome

Gomez, Carolina P; Shio, Marina Tiemi; Olivier, Martin; Descoteaux, Albert . Role of the Protein SHP-1 in the Biogenesis of the Phagolysosome In: 11ième Symposium Annuel de Parasitologie Moléculaire du Québec, 7-8 juin 2011, Université McGill.

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Résumé

The processes of phagocytosis and phagosomal maturation involve the recruitment of effector proteins that participate in phagosome formation and in the acidification and/or fusion with various endocytic vesicles. Among these proteins, phosphatases are known to be involved in such processes (e.g. PTP-MEG-2), and in some cases, are used by intracellular parasites to delay the maturation process to their advantage (e.g. M. tuberculosis). The role of the Src homology 2 domain-containing phosphatase 1 (SHP-1) in this process has yet to be determined. Using murine bone-marrow derived macrophages (BMMs) we showed that SHP-1 is indeed recruited to the nascent phagosome and colocalizes with the Lysosomal-associated membrane protein 1 (LAMP1), a marker of phagosomal maturation. To evaluate the impact of SHP-1 on phagosome biology, we used macrophage cell lines deficient for SHP-1 (motheaten [me SHP-1-/-]), and their wild type littermate (LM) as a control. We studied the kinetics of the recruitment of LAMP1 and Cathepsin D (CathD) in presence or absence of SHP-1. Using confocal microscopy and Western blotting analyses, we noticed a delayed recruitment in SHP-1-/- cells for LAMP-1, as well as for other markers such Cath D and Flotillin-2. Also, we obtained evidence that in the absence of SHP-1, phagosome acidification was impaired. Consistently, acquisition of the proton-vacuolar ATPase (v-ATPase), in our preliminary results, was shown to be impaired in SHP-1-/- cells. Taken together, these results are consistent with a role for SHP1 in the regulation of signaling or membrane fusion events involved in phagolysosome biogenesis

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: 03 mai 2018 15:43
Dernière modification: 03 mai 2018 15:43
URI: http://espace.inrs.ca/id/eprint/7112

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