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ICHIHARA Atsuhiro
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Professor and Division head |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Vacuolar ATPase in phagosome-lysosome fusion. |
| Journal | Formal name：The Journal of biological chemistry Abbreviation：J Biol Chem ISSN code：1083351X(Electronic)00219258(Linking) |
| Volume, Issue, Page | 290(22),pp.14166-80 |
| Author and coauthor | Kissing Sandra†, Hermsen Christina, Repnik Urska, Nesset Cecilie Kåsi, von Bargen Kristine, Griffiths Gareth, Ichihara Atsuhiro, Lee Beth S, Schwake Michael, De Brabander Jef, Haas Albert, Saftig Paul |
| Publication date | 2015/05 |
| Summary | The vacuolar H(+)-ATPase (v-ATPase) complex is instrumental in establishing and maintaining acidification of some cellular compartments, thereby ensuring their functionality. Recently it has been proposed that the transmembrane V0 sector of v-ATPase and its a-subunits promote membrane fusion in the endocytic and exocytic pathways independent of their acidification functions. Here, we tested if such a proton-pumping independent role of v-ATPase also applies to phagosome-lysosome fusion. Surprisingly, endo(lyso)somes in mouse embryonic fibroblasts lacking the V0 a3 subunit of the v-ATPase acidified normally, and endosome and lysosome marker proteins were recruited to phagosomes with similar kinetics in the presence or absence of the a3 subunit. Further experiments used macrophages with a knockdown of v-ATPase accessory protein 2 (ATP6AP2) expression, resulting in a strongly reduced level of the V0 sector of the v-ATPase. However, acidification appeared undisturbed, and fusion between latex bead-containing phagosomes and lysosomes, as analyzed by electron microscopy, was even slightly enhanced, as was killing of non-pathogenic bacteria by V0 mutant macrophages. Pharmacologically neutralized lysosome pH did not affect maturation of phagosomes in mouse embryonic cells or macrophages. Finally, locking the two large parts of the v-ATPase complex together by the drug saliphenylhalamide A did not inhibit in vitro and in cellulo fusion of phagosomes with lysosomes. Hence, our data do not suggest a fusion-promoting role of the v-ATPase in the formation of phagolysosomes. |
| DOI | 10.1074/jbc.M114.628891 |
| PMID | 25903133 |