Commentary: Granins, Secretory Granule Biogenesis, and Transport

Abstract

Secretory granules are the hallmark of secretory cells that secrete granins, peptide hormones, and enzymes for various physiological functions in endocrine, exocrine, and neurons. The granin family of proteins are highly acidic and are the major components in dense core secretory granules, including those in chromaffin cells. Granins include chromogranin (Cg) A, B, and secretogranin (Sg) II which are processed to various derived peptides. In this 16th International Symposium of Chromaffin Cell Biology, a number of papers focusing on the mechanisms of biogenesis and transport of secretory granules in chromaffin cells, other endocrine cells and astrocytes were presented. As well, new physiological roles of granin-derived peptides were discussed. Maite Montero-Hadjadje (France) demonstrated that via its terminal domains, CgA induced granule biogenesis and generated a regulated secretory pathway in fibroblasts. These granules recruited cytoskeletal proteins, actin/myosin and microtubule motors to their surface and exhibited Ca sensitive transport to the plasma membrane for release. Peng Loh (USA) showed that a C-terminal CgA-derived peptide, serpinin, upon being released after stimulation of the cells, upregulated the transcription of a protease inhibitor, protease nexin-1 (PN-1) in a cAMP-PKA-sp1 dependent pathway. This in turn stabilized and augmented the level of granule proteins in the Golgi complex, leading to enhanced granule biogenesis. Ricardo Borges (Spain) using chromaffin cells from CgA knockout (KO), CgB KO and Cg double KO mice showed that the absence of granins led to changes in the accumulation and secretion of catecholamines. They concluded that these Cgs are highly efficient in facilitatingmonoamine and calcium accumulation and in the kinetics of exocytosis of dense core granules (for more details, see review by Borges group below). Seung Yoo (Korea) demonstrated the presence of inositol 1,4,5, triphosphate (IP3) sensitive Ca stores and three forms of IP3 receptors/channels in secretory granules in astrocytes, that presumably interacts with the Cgs to modulate Ca channels and Ca release as in chromaffin granules. Several papers were presented demonstrating the role of cytoskeletal network/proteins in granule transport to the plasma membrane for exocytosis. Luis Gutierrez (Spain) presented confocal microscopy and 3D reconstructed images revealing the complex F-actin structure at the cortex of chromaffin cells. He showed that this F-actin structure underwent reorganization during secretion to reposition the vesicles for exocytosis, (for more details, see their review below). Heidi de Wit (The Netherlands) recapped her extensive studies on the morphology of synaptic protein knockout cells at the electron microscopy level, suggesting that syntaxin, SNAP25 and synaptogamin form the minimal docking machinery. She also discussed the role of Munc 18 in reorganizing cortical F-actin for vesicle docking at the plasma membrane, prior to secretion, in chromaffin cells of embryonic mice. (See her review below). Frederic Meunier (Australia) described a novel phosphatidylinisitol (4,5) biphosphate pathway that controls actin-mediated mobilization and translocation of secretory vesicles to the plasma membrane. Small GTPases such as the Rho GTPase family are involved in actin remodeling during exocytosis. Stephane Gasman (France) showed in chromaffin cells and PC12 cells that Rho A, which is associated with secretory Y. P. Loh (*) Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA e-mail: lohp@mail.nih.gov