Posttranslational processing of proenkephalins and chromogranins/secretogranins

Posttranslational processing of peptide-precursors is nowadays believed to play an important role in the functioning of neurons and endocrine cells. Both proenkephalins and chromogranins/secretogranins are considered as precursor molecules in these tissues, resulting in posttranslationally formed degradation products with potential biological activities. Among the proteins and peptides of neuronal and endocrine secretory granules, the enkephalins and enkephalin-containing peptides have been most extensively studied. The characterization of the post-translationally formed degradation products of the proenkephalins have enabled the understanding of their processing pathway. Chromogranins/secretogranins represent a group of acidic glycoproteins, contained within hormone storage granules. The biochemistry, biogenesis and molecular properties of these proteins have already been studied for 25 years. The chromogranins/secretogranins have a widespread distribution throughout the neuroendocrine system, the adrenal medullary chromaffin granules being the major source of these storage components. Recent data provide evidence for a precursor role for all members of the chromogranins/secretogranins family although also several other functions have been proposed. In this review, some of the methods applied to study proteolytic processing are described. In addition, the posttranslational processing of chromogranins/secretogranins and proenkephalins, especially the biochemical aspects, will be discussed and compared. Recent exciting developments on the generation and identification of potential physiologically active fragments will be covered.