BIOGENESIS OF SECRETORY GRANULES IN THE TRANS-GOLGI NETWORK OF NEUROENDOCRINE AND ENDOCRINE-CELLS

Secretory granule formation requires selection of soluble and membrane proteins into nascent secretory granules, and exclusion of proteins n ot required for the function of secretory granules. Both selection and exclusion presumably can occur in the compartment where assembly of t he secretory granule begins, the trans most cisternae of the Golgi com plex. Current research focused on the initial stages of secretory gran ule formation includes a search for the 'signals' which may mediate ac tive sorting of components into secretory granules, and the role of ag gregation of regulated secretory proteins in sorting. In addition, the temporal sequence of the sorting events in the Golgi, and post-Golgi compartments has gained much attention, as summarized by the alternati ve but not mutually exclusive 'sorting for entry' vs. 'sorting by rete ntion' models. 'Sorting for entry' which encompasses the most popular models requires selection of cargo and membrane and exclusion of non-s ecretory granule proteins in the TGN prior to secretory granule format ion. 'Sorting by retention' stipulates that protein selection or exclu sion may occur after secretory granule formation: secretory granule sp ecific components are retained during maturation of the granule while non-secretory granule molecules are removed in vesicles which bud from maturing secretory granules. Finally, some progress has been made in the identification of cytosolic components involved in the budding of nascent secretory granules from the TGN. This review will focus on the recent data concerning the events in secretory granule formation whic h occur, in the trans-Golgi network. (C) 1998 Elsevier Science B.V. Al l rights reserved.