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

The molecular signals that target a polypeptide hormone to the regulated secretory pathway are poorly understood, although morphological evidence has implicated selective aggregation or precipitation, initiated in the TGN, in the sorting process (44) . Current evidence suggests that in the absence of a specific topogenic signal, e.g., for retention in the ER (27, 34) or Golgi apparatus (19) or for sorting to lysosomes (16) , secretion through the constitutive pathway oc-curs by default (14, 36) . Expression of heterologous precursors in different endocrine cell lines results in proteolytic cleavage to the mature hormone and, in some cases, targeting to the regulated secretory pathway; e.g., preproinsulin (26) , pretrypsinogen (5) , preproenkephalin (43) , preprorenin (10) , preproneuropeptide Y (8) , and preprosomatostatin (39, 41) . Since this diverse group of proteins, which lack amino acid sequence homology, can be sorted to the regulated secretory pathway, it is likely that a common structural feature rather than a primary sequence is involved in targeting. However, the identity of putative sorting signals has been elusive.