Secretory granule biogenesis: rafting to the SNARE

Regulated secretion of hormones occurs when a cell receives an external sti mulus, triggering the secretory granules to undergo fusion with the plasma membrane and release their content into the extracellular milieu. The forma tion of a mature secretory granule (MSG) involves a series of discrete and unique events such as protein sorting, formation of immature secretory gran ules (ISGs), prohormone processing and vesicle fusion. Regulated secretory proteins (RSPs), the proteins stored and secreted from MSGs, contain signal s or domains to direct them into the regulated secretory pathway. Recent da ta on the role of specific domains in RSPs involved in sorting and aggregat ion suggest that the cell-type-specific composition of RSPs in the trans-Go lgi network (TGN) has an important role in determining how the RSPs get int o ISGs. The realization that lipid rafts are implicated in sorting RSPs in the TGN and the identification of SNARE molecules represent further major a dvances in our understanding of how MSGs are formed. At the heart of these findings is the elucidation of molecular mechanisms driving protein-lipid a nd protein-protein interactions specific for secretory granule biogenesis.