The granin family--its role in sorting and secretory granule formation

Two types of secretory pathways are present in mammalian cells: constitutive secretion and regulated secretion (1). In the constitutive secretory pathway, which is found in all types of cells, secretory products are packed in small vesicles. Most of the proteoglycans and glycoproteins of the extracellular matrix are secreted in this way. The regulated secretory pathway, found in the more differentiated secretory cells, is mediated by specialized secretory granules. Hormones and neuropeptides are secreted in this way. Both the constitutive and regulated secretory pathways emanate from the trans-Golgi network (TGN). Recent studies have indicated that the granin family (secretogranins/chromogranins) plays an important role in the sorting and aggregation of secretory products in the trans-Golgi network (TGN), and in the subsequent formation of secretory granules. The granin family is thought to be one of the mediators of the regulated secretory pathway (2-6). This family is widely expressed in endocrine (7-9) and neuronal cells (10-12), where they are stored in secretory granules together with various peptide hormones and neuropeptides. Three acidic sulfated proteins, chromogranin A (Cg A), secretogranin I (Sg I; also called chromogranin B; Cg B), and secretogranin II (Sg II) are well known as the major proteins in the family. Recently, three acidic secretory proteins, 1B1075 gene product (13), HISL-19 antigen (14) and 7B2 (15), have been thought to be members of the granin family, accordingly termed as Sg III, Sg IV and Sg V, respectively. However, it still remains open to discussion whether 1B1075 gene product, the HISL-19 antigen and 7B2 are true members of the granin family. In this review, the possible roles of granin family, especially Cg A, Sg I (Cg B) and Sg II in the regulated secretory pathway are discussed, focusing on the sorting, aggregation of proteins in the TGN, and subsequent secretory granule formation.