Aggregation chaperones enhance aggregation and storage of secretory proteins in endocrine cells

calcium-induced aggregation has been proposed to play a role in the sorting and storage of secretory proteins in secretary granules of endocrine cells . The regulation of this process is not known. Hexahistidine epitope tags w ere used to create aggregation chaperones that enhance the calcium-induced aggregation of secretary granule proteins in vitro. Indeed, 100% recovery o f the aggregating target protein was achieved without any modification of t he target protein. The aggregation chaperone is not trapped in the aggregat es. Go-expression of His(6)-tagged secreted alkaline phosphatase and the re gulated secretory protein chromogranin A resulted in an increased chromogra nin storage in secretary granules, and stimulated secretion of chromogranin A increased 50%. However, secretion of secreted alkaline phosphatase was n ot affected by the hexahistidine epitope tag. Thus, calcium-induced aggrega tion is not a passive process; rather, aggregation and sorting of secretory proteins can be regulated by aggregation chaperones in the secretary pathw ay of endocrine cells.