THE BIOSYNTHESIS AND PROCESSING OF NEUROENDOCRINE PEPTIDES - IDENTIFICATION OF PROPROTEIN CONVERTASES INVOLVED IN INTRAVESICULAR PROCESSING

This chapter discusses recent advances in the understanding of how proinsulin and other precursor proteins are processed into their biologically active products. The newly-formed secretory vesicles derived from the golgi complex appear to be the main site of precursor processing in both β cells and peptidergic neurones. The insulin-producing β cells are highly specialized secretory cells that share many properties with other neuroendocrine cells and have a number of additional specialized features attributable to their unique chemosensory functions. The chapter proposes to isolate two complementary DNAs (cDNAs) from a human insulinoma and mouse pituitary AtT20 cells that encode serine proteases (PC2 and PC3) having catalytic domains homologous to those of the bacterial substilisins and Kex2, a yeast proα-factor processing endoprotease. These enzymes appear to be designed to function in an acidic environment enriched in calcium ions as is believed to exist in maturing neuroendocrine secretory vesicles. Available evidence suggests that PC2 and PC3 as well as furin, a trans Golgi associated Kex2-like protease, are members of a hitherto unrecognized and ancient superfamily of subtilisin-related proteinases in eukaryotic cells that are involved in the intracellular processing of precursor proteins. © 1992, Academic Press Inc.