title: The protein tyrosine phosphatase SHP-1 regulates phagolysosome biogenesis.
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.
authors: Institut National de la Recherche Scientifique-Institut Armand-Frappier, Laval, Quebec H7V 1B7, Canada.
authors: Carolina P
authors: CP
authors: Gómez
authors: Marina
authors: M
authors: Tiemi Shio
authors: Pascale
authors: P
authors: Duplay
authors: Martin
authors: M
authors: Olivier
authors: Albert
authors: A
authors: Descoteaux
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D002461:Cell Line, Transformed; D005260:Female; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D010588:Phagosomes / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000172:deficiency / Q000502:physiology*
chemical_list: D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse