ATPase, H+ Transporting, Lysosomal 38kDa, V0 Subunit D2 (ATP6V0D2)

Atp6v0d2 (d2), showed 5-fold higher expression than that of Atp6v0d1 (d1) in mature osteoclasts, indicating a potential function in osteoclastic bone resorption. When d2 was depleted at an early stage of RANKL-induced osteoclast differentiation in vitro, formation of multinucleated cells was severely impaired. Depletion of d2 at a late differentiation stage did not affect osteoclast fusion but did abolish the activity of extracellular acidification and bone resorption of mature osteoclasts. The association of the two tagged-proteins d2 and a3 when co-expressed in mammalian cells with a co-immunoprecipitation assay. Glutathione-S-transferase (GST) pull-down assay showed the direct interaction of d2 with the N terminus of Atp6v0a3 (a3), which is the functionally identified osteoclast-specific component of V-ATPase.