Intermediates in the constitutive and regulated secretory pathways released in vitro from semi-intact cells

Figure 9 A maturation model of secretory granule formation . The TGN where sulfation occurs is represented on the left, the plasma membrane on the right . Proteoglycans are represented by the branched tree, and the regulated secretory proteins (chromogranin B and secretogranin II) by the shaded diamonds and shaded core of secretory granules on the lower right . In the model, the secretory granule precursor after formation is large and light in density. During maturation it loses membrane to become more dense. Maturation by budding might also improve the sorting efficiency by removing material that is excluded from the condensed core. If such budding does occur, the vesicles could return to the Golgi, fuse with the cell surface, or both. As the vesicles mature, they become associated with the cytoskeleton and cannot escape from the cell . (Kelly, 1985 ; von Zastrow and Castle, 1987; von Zastrow et al ., 1989 ) . If small vesicles bud off, they should contain soluble proteins excluded from the proteinaceous core (Fig . 9) , and the ratio of the regulated marker, secretogranin 11, to the constitutive one, sulfated proteoglycan should increase in the granules during granule maturation . Consistent with the latter prediction, the ratio of the two markers does increase during a chase (Fig . 8 B) . Although the model outlined in Fig. 9 is consistent with the data, alternative explanations cannot be eliminated . In particular, it is important to show that newly synthesized proteoglycans and secretogranin II are actually in the same membranous intermediate .