Biosynthesis and characterization of the brain-specific membrane protein DPPX, a dipeptidyl peptidase IV-related protein

Dipeptidyl peptidase IV-related protein (DPPX) was found to be preferential ly expressed in the brain tissue. We isolated two rat cDNA clones encoding DPPX-S and DPPX-L from a brain cDNA library, of which DPPX-L had a longer s equence at the NH2 terminus. The biosynthesis of DPPXs was examined in both in vitro and in vivo systems. In the cell-free translation system, DPPX-S and DPPX-L were synthesized as 93-kDa and 97-kDa forms, respectively, which are in good agreement with the molecular masses estimated from their prima ry structure. In COS-1 cells transfected with the cDNAs, DPPX-S and DPPX-L were initially synthesized as 113-kDa and 117-kDa forms, respectively, with high-mannose type oligosaccharides, which were then converted to 115-kDa a nd 120-kDa forms, mostly with the complex-type sugar chains. Immunofluoresc ence-microscopic observations confirmed that both DPPXs were expressed on t he cell surface. DPPXs were found to have no enzyme activity of DPPIV, even when they were mutated to have the consensus active-site sequence Gly-X-Se r-X-Gly for serine proteases. Immunoblot analysis of samples prepared from various rat tissues demonstrated that DPPX-S, but not DPPX-L, was detectabl e only in the brain tissue. These results indicate that, of the two isoform s, DPPX-S is preferentially expressed in the brain tissue as the surface gl ycoprotein without protease activity, although its function remains unknown at present.