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The formation of secretory vesicles. (A) Secretory proteins become segregated and highly concentrated in secretory vesicles by two mechanisms. First, they aggregate in the ionic environment of the TGN; often, the aggregates become more condensed as a secretory vesicle matures and its lumen becomes more acidic. Second, clathrin-coated vesicles retrieve excess membrane and lumenal content present in immature secretory vesicles as the secretory vesicles mature. (B) This electron micrograph shows secretory vesicles Forming from the TGN in an insulin-secreting β cell of the 

pancreas. Anti-clathrin antibodies conjugated to gold spheres (black dots) have been used to locate clathrin molecules. The immature secretory vesicles, which contain insulin precursor protein (proinsulin), contain clathrin patches, which are no longer seen on the mature secretory vesicle. (B, courtesy of Lelio Orci.)