The propeptide of preprosomatostatin mediates intracellular transport and secretion of alpha-globin from mammalian cells

The choice of a-globin for use in these experiments was based on previous in vitro (17) and in vivo (40, 42) studies which indicate that t~-globin is competent for translocation across the ER membrane when fused to a signal peptide; furthermore, no degradation of the in vitro-translocated t~-globin was observed (17) . The rapid disappearance of a-globin (t~ = 4-5 min) after cleavage of the signal peptide demonstrated that globin alone did not contain sufficient sorting information to mediate secretion. The site of ot-globin degradation was not determined but its rapid turnover indicated degradation shortly after completion of protein synthesis. The lack of inhibition by chloroquine, a drug that inactivates lysosomal enzymes, suggested that degradation did not occur in a lysosomal compartment. Since globin degradation was inhibited between 16 and 20°C, a temperature which prevents exit from the ER (37) , the site of degradation may be between the ER and "early" Golgi regions. However at present, we cannot exclude the possibility that the degradation process is temperature sensitive; i.e., at low temperatures the proteases are inhibited and/or the substrates are less accessible. Thus, additional experiments are therefore necessary to identify the compartment where proteolysis O c c u r s .