The chromogranins: Their roles in secretion from neuroendocrine cells and as markers for neuroendocrine neoplasia

Chromogranins are the major components of the secretory granules of most neuroendocrine cells. Within the secretory pathway, chromogranins are involved in granulogenesis, and in sorting and processing of secretory protein cargo prior to secretion. Once secreted, they have hormonal, autocrine, and paracrine activities. The chromogranin family includes chromogranins A (CgA) and B (CgB) and secretogranin 11 (Sgll, once called chromogranin C). The related granins NESP55, 7132, secretogranin III/1B 1075 (SgIII), and secretogranin IV/HISL-19 antigen (SgIV), are also sometimes included when considering the chromogranins. While it is useful to consider the granin proteins as a family with many common features, it is also necessary to examine the distinct features and properties of individual members of the granin family to understand fully their functions, employ them efficiently as tissue, serum, and urinary markers for neuroendocrine neoplasia, and develop an evolutionary-biologic perspective on their contribution to mammalian physiology. Recent advances in chromogranin research include establishing the role of CgA in granulogenesis and the role of CgB in nuclear transcription; new biologic activities for CgA-, CgB-, and SgII-derived peptides; and new marker functions for granins and their proteolytically processed products in endocrine neoplasias.