Trafficking/sorting and granule biogenesis in the beta-cell

Proinsulin is packaged into nascent (immature, clathrin-coated) secretory g ranules in the trans-Golgi network (TGN) of the beta-cell along with other granular constituents including the proinsulin conversion enzymes. It is as sumed that such packaging is dependent on an active sorting process, separa ting granular proteins from other secretory or membrane proteins, but the m echanism remains elusive. As granules mature, the clathrin coat is lost, th e intragranular milieu is progressively acidified, and proinsulin is conver ted to insulin and C-peptide. Loss of clathrin is believed to arise by budd ing of clathrin-coated vesicles from maturing granules, carrying with them any inappropriate or unnecessary products and Providing an additional means for refinement of granular content.