Vacuolar ATPase in Phagosome-Lysosome Fusion

Kissing S, Hermsen C, Repnik U, Nesset CK, von Bargen K, Griffiths G, Ichihara A, Lee BS, Schwake M, De Brabander J, Haas A, et al. (2015)
Journal of Biological Chemistry 290(22): 14166-14180.

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Abstract
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 V-0 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 V-0 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 V-0 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 V-0 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.
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Kissing S, Hermsen C, Repnik U, et al. Vacuolar ATPase in Phagosome-Lysosome Fusion. Journal of Biological Chemistry. 2015;290(22):14166-14180.
Kissing, S., Hermsen, C., Repnik, U., Nesset, C. K., von Bargen, K., Griffiths, G., Ichihara, A., et al. (2015). Vacuolar ATPase in Phagosome-Lysosome Fusion. Journal of Biological Chemistry, 290(22), 14166-14180.
Kissing, S., Hermsen, C., Repnik, U., Nesset, C. K., von Bargen, K., Griffiths, G., Ichihara, A., Lee, B. S., Schwake, M., De Brabander, J., et al. (2015). Vacuolar ATPase in Phagosome-Lysosome Fusion. Journal of Biological Chemistry 290, 14166-14180.
Kissing, S., et al., 2015. Vacuolar ATPase in Phagosome-Lysosome Fusion. Journal of Biological Chemistry, 290(22), p 14166-14180.
S. Kissing, et al., “Vacuolar ATPase in Phagosome-Lysosome Fusion”, Journal of Biological Chemistry, vol. 290, 2015, pp. 14166-14180.
Kissing, S., Hermsen, C., Repnik, U., Nesset, C.K., von Bargen, K., Griffiths, G., Ichihara, A., Lee, B.S., Schwake, M., De Brabander, J., Haas, A., Saftig, P.: Vacuolar ATPase in Phagosome-Lysosome Fusion. Journal of Biological Chemistry. 290, 14166-14180 (2015).
Kissing, Sandra, Hermsen, Christina, Repnik, Urska, Nesset, Cecilie Kasi, von Bargen, Kristine, Griffiths, Gareth, Ichihara, Atsuhiro, Lee, Beth S., Schwake, Michael, De Brabander, Jef, Haas, Albert, and Saftig, Paul. “Vacuolar ATPase in Phagosome-Lysosome Fusion”. Journal of Biological Chemistry 290.22 (2015): 14166-14180.
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PMID: 25903133
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