The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells

OST neuropeptides and small peptide hormones are synthesized as part of larger inactive polyprotein precursors in which the hormone sequence is flanked by pairs of basic amino acids (9) . To generate a bioactive molecule, the precursors undergo one or several posttranslational modifications including glycosylation, proteolysis, phosphorylation, amidation, and acetylation (9) . These processing events occur in different organelles during intracellular transport and therefore peptide hormone precursors are useful models to study movement through the secretory pathway. Recent observations demonstrate that several sorting and processing events occur in the distal elements of the Golgi apparatus/trans-Golgi network (TGN) ~ and in maturing secretory granules (12, 29, 30, 44) . In particular, endoproteolytic cleavage at paired basic residues is initiated in acidic, clathrin-coated vesicles which bud from the TGN and the resulting mature hormone is stored in secretory granules (30, 31, 44) .