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Direct recruitment of H+-ATPase from lysosomes for phagosomal acidification

2009; The Company of Biologists; Volume: 122; Issue: 14 Linguagem: Inglês

10.1242/jcs.050443

1477-9137

Ge‐Hong Sun‐Wada, Hiroyuki Tabata, Nobuyuki Kawamura, Minako Aoyama, Yoh Wada,

Lysosomal Storage Disorders Research

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.