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

An alternative, or at least additional, cause for aggregation in the TGN is a change in the lumenal milieu in this compartment as compared tothe more proximal compartments ofthe secretory pathway (Burgess and Kelly, 1987; Pfeffer and Rothman, 1987; Huttner et al., 1988'; Gerdes et al.,' 1989) . One parameter of the lumenal milieu that is known to differ between the RER and the TGN is the pH; the TGN has been shown to be moderately acidic . From the data available (see Anderson and Orci, 1988, and refs. therein) , the TGN lu-menalpH can be estimated to be -1 U above that ofneuroendocrine secretory granules (pH 5.2-5.5; Poisnet andTrifaro, 1982; Johnson, 1987) , i.e., around pH 6.4, a value consis-tent with previous considerations (Griffiths and Simons, 1986) . Another parameter is the concentration of calcium ions. Studies in various regulated secretory cells (Stoeckel et al., 1975; Ravazzola, 1976; Mata et al., 1987; Roos, 1988) have shown that the calcium concentration in the Golgi complex is significantly higher (N2 .5-fold) than in the RER which is believed to contain 3 mM calcium (Sambrook : 1990) , and two-thirds of that found in secretory granules, which havebeen shown to contain 20-50 mM calcium (Poisner and Trifaro, 1982; Bulenda and Gratzl, 1985) . These observations suggest that the lumenal milieu of the TGN differs from that of the more proximal compartments of the secretory pathway in that it contains a higher concentration of calcium ions (probably around 10 mM total calcium ; see Discussion for "free" vs. "bound" calcium) . The selective aggregation ofregulated, but not constitutive, secretory proteins in the TGN may therefore reflect the inherent property of the former, but not the latter, proteins to come out of solution upon a change in certain parameters of the lumenal milieu such as pH and calcium ion concentration.