ABSTRACT
This chapter outlines current knowledge regarding the intracellular processes that govern the ultimate release of active renin, in the context of recent information about the mechanism of secretion of other mammalian proteins. Targeting of proteins to the lumen of lysosomes requires two intracellular recognition events. The first is the phosphorylation of mannose residues on N-linked oligosaccharides. In cathepsin D, a lysosomal aspartyl protease, a lysine residue and a noncontiguous 27-amino acid peptide sequence contained in a surface loop of the protein are required for recognition by the phosphotransferase. AtT-20 cells transfected with a human preprorenin expression vector also cleave prorenin at the same site as that reported for renin purified from human kidney lysates. One hypothesis to explain the cleavage site selectivity displayed by enzymes in vitro, AtT-20 cells, and the kidney is that primary and/or higher-order structural determinants on prorenin render the native processing site uniquely sensitive to proteolytic cleavage.
