Direct recruitment of H+-ATPase from lysosomes for phagosomal acidification
- PMID: 19549681
- DOI: 10.1242/jcs.050443
Direct recruitment of H+-ATPase from lysosomes for phagosomal acidification
Abstract
The nascent phagosome progressively establishes an acidic milieu by acquiring a proton pump, the vacuolar-type ATPase (V-ATPase). However, the origin of phagosomal V-ATPase remains poorly understood. We found that phagosomes were enriched with the V-ATPase a3 subunit, which also accumulated in late endosomes and lysosomes. We modified the mouse Tcirg1 locus encoding subunit a3, to express an a3-GFP fusion protein. Live-cell imaging and immunofluorescence microscopy revealed that nascent phagosomes received the a3-GFP from tubular structures extending from lysosomes located in the perinuclear region. Macrophages from a3-deficient mice exhibited impaired acidification of phagosomes and delayed digestion of bacteria. These results show that lysosomal V-ATPase is recruited directly to the phagosomes via tubular lysosomes to establish the acidic environment hostile to pathogens.
Similar articles
-
Yersinia pseudotuberculosis blocks the phagosomal acidification of B10.A mouse macrophages through the inhibition of vacuolar H(+)-ATPase activity.Microb Pathog. 1999 Oct;27(4):253-63. doi: 10.1006/mpat.1999.0303. Microb Pathog. 1999. PMID: 10502466
-
Regulation of the macrophage vacuolar ATPase and phagosome-lysosome fusion by Histoplasma capsulatum.J Immunol. 1999 May 15;162(10):6148-54. J Immunol. 1999. PMID: 10229858
-
Bafilomycin A1 inhibits lysosomal, phagosomal, and plasma membrane H(+)-ATPase and induces lysosomal enzyme secretion in macrophages.J Cell Physiol. 1995 Apr;163(1):137-44. doi: 10.1002/jcp.1041630116. J Cell Physiol. 1995. PMID: 7896890
-
Vacuolar ATPase in phago(lyso)some biology.Int J Med Microbiol. 2018 Jan;308(1):58-67. doi: 10.1016/j.ijmm.2017.08.007. Epub 2017 Sep 1. Int J Med Microbiol. 2018. PMID: 28867521 Review.
-
The little we know on the structure and machinery of V-ATPase.J Exp Biol. 2009 Jun;212(Pt 11):1604-10. doi: 10.1242/jeb.025866. J Exp Biol. 2009. PMID: 19448070 Review.
Cited by
-
Vacuolar ATPase in phagosome-lysosome fusion.J Biol Chem. 2015 May 29;290(22):14166-80. doi: 10.1074/jbc.M114.628891. Epub 2015 Apr 22. J Biol Chem. 2015. PMID: 25903133 Free PMC article.
-
Rab32 and Rab38 maintain bone homeostasis by regulating intracellular traffic in osteoclasts.Cell Struct Funct. 2023 Nov 17;48(2):223-239. doi: 10.1247/csf.23061. Epub 2023 Nov 10. Cell Struct Funct. 2023. PMID: 37793839 Free PMC article.
-
Importance of phagosomal functionality for growth restriction of Mycobacterium tuberculosis in primary human macrophages.J Innate Immun. 2011;3(5):508-18. doi: 10.1159/000325297. Epub 2011 May 11. J Innate Immun. 2011. PMID: 21576918 Free PMC article.
-
Insights into innovative therapeutics for drug-resistant tuberculosis: Host-directed therapy and autophagy inducing modified nanoparticles.Int J Pharm. 2022 Jun 25;622:121893. doi: 10.1016/j.ijpharm.2022.121893. Epub 2022 Jun 6. Int J Pharm. 2022. PMID: 35680110 Free PMC article.
-
V-ATPase and osmotic imbalances activate endolysosomal LC3 lipidation.Autophagy. 2015;11(1):88-99. doi: 10.4161/15548627.2014.984277. Autophagy. 2015. PMID: 25484071 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
