%0 Journal Article %T The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis. %+ Institut Armand Frappier (INRS-IAF) %+ Center for Host-Parasite Interactions %+ Department of Medicine, Centre for the Study of Host Resistance %+ Department of Microbiology and Immunology [Montréal] %A Gómez, Carolina P %A Tiemi Shio, Marina %A Duplay, Pascale %A Olivier, Martin %A Descoteaux, Albert %< avec comité de lecture %@ 0022-1767 %J Journal of Immunology %I Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists %V 189 %N 5 %P 2203-10 %8 2012-09-01 %D 2012 %R 10.4049/jimmunol.1103021 %M 22826316 %Z Life Sciences [q-bio]/Human health and pathology/Infectious diseasesJournal articles %X The process of phagocytosis and phagosome maturation involves the recruitment of effector proteins that participate in phagosome formation and in the acidification and/or fusion with various endocytic vesicles. In the current study, we investigated the role of the Src homology region 2 domain-containing phosphatase 1 (SHP-1) in phagolysosome biogenesis. To this end, we used immortalized bone marrow macrophages derived from SHP-1-deficient motheaten mice and their wild-type littermates. We found that SHP-1 is recruited early and remains present on phagosomes for up to 4 h postphagocytosis. Using confocal immunofluorescence microscopy and Western blot analyses on purified phagosome extracts, we observed an impaired recruitment of lysosomal-associated membrane protein 1 in SHP-1-deficient macrophages. Moreover, Western blot analyses revealed that whereas the 51-kDa procathepsin D is recruited to phagosomes, it is not processed into the 46-kDa cathepsin D in the absence of SHP-1, suggesting a defect in acidification. Using the lysosomotropic agent LysoTracker as an indicator of phagosomal pH, we obtained evidence that in the absence of SHP-1, phagosome acidification was impaired. Taken together, these results are consistent with a role for SHP-1 in the regulation of signaling or membrane fusion events involved in phagolysosome biogenesis. %G English %2 https://riip.hal.science/pasteur-01001767/document %2 https://riip.hal.science/pasteur-01001767/file/Descoteaux_A_22826316.pdf %L pasteur-01001767 %U https://riip.hal.science/pasteur-01001767 %~ RIIP %~ INRS-IAF