The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis. - Archive ouverte HAL Access content directly
Journal Articles Journal of Immunology Year : 2012

The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis.

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Abstract

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.
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Dates and versions

pasteur-01001767 , version 1 (04-06-2014)

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Carolina P Gómez, Marina Tiemi Shio, Pascale Duplay, Martin Olivier, Albert Descoteaux. The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis.. Journal of Immunology, 2012, 189 (5), pp.2203-10. ⟨10.4049/jimmunol.1103021⟩. ⟨pasteur-01001767⟩

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