HETEROGENEITY OF VACUOLAR H-ATPASE - DIFFERENTIAL EXPRESSION OF 2 HUMAN SUBUNIT B-ISOFORMS()

The catalytic domain of the vacuolar proton ATPase is composed of a he xamer of three A subunits and three B subunits. Here we describe the c loning and characterization of a cDNA isoform of subunit B, HO57, from an osteoclastoma cDNA library. HO57 is represented by three species o f mRNA of 1.6, 2.6 and 2.8 kb and is expressed at low levels in a rang e of human tissues, but at significantly higher levels in brain, kidne y and osteoclastoma, and is probably an ubiquitously expressed isoform . In contrast, the kidney-specific isoform has an mRNA of 2kb and is s pecifically expressed al high levels only in kidney and, at a lower le vel, in placenta. Thus the HO57 isoform is integral to the vacuolar AT Pase found in the general secretory system of all cells as well as in vacuolar-ATPase-rich sources such as neurones and osteoclasts, whereas both the kidney-specific isoform and HO57 are highly expressed in the kidney. Furthermore, we show by in situ hybridization that HO57 is th e only isoform that is exclusively and highly expressed by osteoclasts .