Three subunit a isoforms of mouse vacuolar H+-ATPase - Preferential expression of the a3 isoform during osteoclast differentiation

Vacuolar H+-ATPase CV-ATPase) is a multi-subunit enzyme with a membrane per ipheral catalytic (V-1) and an intrinsic (V-o) sector. We have identified t hree cDNA clones coding for isoforms of mouse V-o subunit a (a1, a2, and a3 ). They exhibit 48-52% identity with each other and high similarity to subu nit a of other species. The al isoform was mainly expressed in brain and li ver. The a2 isoform was observed in heart and kidney in addition to brain a nd Liver. Transcripts for the a3 isoform were strongly expressed in heart a nd liver. The a3 isoform was induced during osteoclast differentiation, and localized in the plasma membrane and cytoplasmic filamentous structures. I n contrast to a3, the a1 isoform was constitutively expressed and localized in the cytoplasmic endomembrane compartments of the same cells. These find ings suggest that the a3 isoform is a component of the plasma membrane V-AT Pase essential for bone resorption.