INVOLVEMENT OF MOLECULAR CHAPERONES IN THE ABERRANT AGGREGATION OF SECRETORY PROTEINS IN PANCREATIC ACINAR-CELLS

Molecular chaperones have recently been shown to be accurately located along distinct cellular compartments of the secretory pathway of panc reatic acinar cells. Since the aberrant aggregation of secretory prote ins leading to the formation of RER intracisternal crystals induced by DL-p-chlorophenylalanine methyl ester (CPME) comprises major changes in the sorting, selective transport, and/or posttranslational modifica tions of secretory proteins, we decided to investigate the possible in volvement of chaperones in this phenomenon by applying the protein A-g old immunocytochemical approach. In addition to their presence in the cellular compartments of the secretory pathway, the chaperonins cpn10 and cpn60 were found to also be concentrated in the RER intracisternal crystals. In contrast, the hsp70 protein remained confined to the tra ns-Golgi network and was absent from the crystals. In both control and experimental conditions the three chaperones were present in mitochon dria. Quantitative evaluations confirmed these observations and reveal ed an overall decrease in the labeling, particularly for hsp70 after C PME treatment. These labeling patterns suggest a participation of the chaperonins cpn10 and cpn60 but not of the hsp70 in the aberrant aggre gation of secretory proteins leading to RER crystal formation. The rol e played by chaperones in this process, however, remains to be elucida ted. (c) 1994 Academic Press, Inc.