title: Large dense-core secretory granule biogenesis is under the control of chromogranin A in neuroendocrine cells.
abstract: The large dense-core secretory granule is an organelle in neuroendocrine/endocrine cells, where prohormones and proneuropeptides are stored, processed, and secreted in a regulated manner. Here we present evidence that chromogranin A (CgA), one of the most abundant acidic glycoproteins ubiquitously present in neuroendocrine/endocrine cells, regulates dense-core secretory granule biogenesis. Specific depletion of CgA expression by antisense RNAs in PC12 cells led to a profound loss of secretory granule formation. An exogenously expressed prohormone, pro-opiomelanocortin, was neither stored nor secreted in a regulated manner in CgA-deficient PC12 cells. Overexpression of bovine CgA into CgA-deficient PC12 cells rescued regulated secretion. Other secretory granule proteins, such as chromogranin B (CgB), carboxypeptidase E, and synaptotagmin, were rapidly degraded, whereas nongranule proteins were not affected in CgA-deficient PC12 cells. Unlike CgA, another granin protein CgB could not substitute for the role of CgA in secretory granule biogenesis. Thus, we conclude that CgA is a master "on/off" switch regulating the formation of the dense-core secretory granule in neuroendocrine cells.
authors.affiliation: Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. tkim@codon.nih.gov
authors.forename: Taeyoon
authors.initials: T
authors.lastname: Kim
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Tao-Cheng
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
authors.forename: Y Peng
authors.initials: YP
authors.lastname: Loh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002135:Calcium-Binding Proteins; D043423:Carboxypeptidase H; D002268:Carboxypeptidases / Q000378:metabolism; D053379:Chromogranin A; D002864:Chromogranins / Q000378:metabolism / Q000502:physiology*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D050857:Synaptotagmins
chemical_list: D002135:Calcium-Binding Proteins; D053379:Chromogranin A; D002864:Chromogranins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D016376:Oligonucleotides, Antisense; C506153:chromogranin A, rat; D050857:Synaptotagmins; D002268:Carboxypeptidases; D043423:Carboxypeptidase H