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Large Dense‐Core Secretory Granule Biogenesis Is under the Control of Chromogranin A in Neuroendocrine Cells
Author(s) -
KIM TAEYOON,
TAOCHENG JUNGHWA,
EIDEN LEE E.,
LOH Y. PENG
Publication year - 2002
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2002.tb04487.x
Subject(s) - chromogranin a , granule (geology) , enteroendocrine cell , secretory protein , secretion , microbiology and biotechnology , biogenesis , secretory vesicle , biology , neuroendocrine cell , exocytosis , medicine , endocrinology , endocrine system , biochemistry , immunology , hormone , gene , paleontology , immunohistochemistry
A bstract : 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.