Three Subunit a Isoforms of Mouse Vacuolar H+-ATPase

Abstract

Vacuolar H+-ATPase (V-ATPase) is a multi-subunit enzyme With a membrane peripheral catalytic (V1) and an intrinsic (V(o)) sector. We have identified three cDNA clones coding for isoforms of mouse V(o) subunit a (α1, α2, and α3). They exhibit 48-52% identity with each other and high similarity to subunit a of other species. The α1 isoform was mainly expressed in brain and liver. The α2 isoform was observed in heart and kidney in addition to brain and liver. Transcripts for the α3 isoform were strongly expressed in heart and liver. The α3 isoform was induced during osteoclast differentiation, and localized in the plasma membrane and cytoplasmic filamentous structures. In contrast to α3, the α1 isoform was constitutively expressed and localized in the cytoplasmic endomembrane compartments of the same cells. These findings suggest that the α3 isoform is a component of the plasma membrane V-ATPase essential for bone resorption.