Milieu-induced, selective aggregation of regulated secretory proteins in the trans-Golgi network

Interestingly, aggregative milieu did not interfere with the release of GAG chains, a constitutively secreted bulk flow marker, from the permeabilized TGN vesicles, showing that these molecules were excluded from the granin aggregates under these conditions. Granins isolated from secretory granules have previously been found to form aggregates at granule-like pH (pH 5.2-5.9 ) which excluded various constitutive secretory proteins (Gerdes et al., 1989; Gorr et al., 1989; Hutmer et al., 1991) . The present data extend these in vitro observations to the compartment relevant for sorting, the TGN . Our results support the hypothesis that the selective aggregation of regulated secretory proteins in the TGN is a crucial step in their segregation from constitutive secretory proteins and suggest that, in the case of the granins, a decrease in pH and an increase in calcium, i.e., a change in milieu towards a TGN-like condition, are sufficient to trigger this aggregation process .