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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Large dense-core secretory granule biogenesis is under the control of chromogranin A in neuroendocrine cells.

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.[1]


  1. Large dense-core secretory granule biogenesis is under the control of chromogranin A in neuroendocrine cells. Kim, T., Tao-Cheng, J.H., Eiden, L.E., Loh, Y.P. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
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