Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis
Open accessAbstract
We present evidence that regulation of dense-core secretory granule biogenesis and hormone secretion in endocrine cells is dependent on chromogranin A (CGA). Downregulation of CGA expression in a neuroendocrine cell line, PC12, by antisense RNAs led to profound loss of dense-core secretory granules, impairment of regulated secretion of a transfected prohormone, and reduction of secretory granule proteins. Transfection of bovine CGA into a CGA-deficient PC12 clone rescued the regulated secretory phenotype. Stable transfection of CGA into a CGA-deficient pituitary cell line, 6T3, lacking a regulated secretory pathway, restored regulated secretion. Overexpression of CGA induced dense-core granules, immunoreactive for CGA, in nonendocrine fibroblast CV-1 cells. We conclude that CGA is an "on/off" switch that alone is sufficient to drive dense-core secretory granule biogenesis and hormone sequestration in endocrine cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chga plays a key role in the formation of dense-core granules.
“Chga plays a key role in the formation of DCGs (Kim et al., 2001).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Kim et al., 2001
Chga regulates the biogenesis of catecholamine-containing DCGs in the adrenal gland.
“Chga has been shown to regulate the biogenesis of catecholamine-containing DCGs in the adrenal gland (Díaz-Vera et al., 2012; Kim et al., 2001; Pasqua et al., 2016).”
From Intestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells (2021) · cites this paper as Kim et al., 2001
Cites
The chromogranins A and B: The first 25 years and future perspectives
Winkler, H. J. S., & Fischer‐Colbrie, R. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90222-n · Cited by 663 · see citing works
The granin-(chromogranin/secretogranin) family
Huttner, W. Β., Gerdes, H. H., & Rosa, P. (1991) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(91)90012-k · Cited by 480 · see citing works
Cool, D. R., Normant, E., Shen, F.-S., Chen, H., Pannell, L. K., Zhang, Y., & Loh, Y. P. (1997) · Cell · doi:10.1016/s0092-8674(00)81860-7 · Cited by 449 · see citing works
Self-citationHeparin is essential for the storage of specific granule proteases in mast cells
Humphries, D. E., Wong, G. W., Friend, D. S., Gurish, M. F., Qiu, W.-T., Huang, C. B., Sharpe, A. H., & Stevens, R. L. (1999) · Nature · doi:10.1038/23481 · Cited by 428 · see citing works
Gerdes, H. H., Rosa, P., Phillips, E., Baeuerle, P. A., Frank, R. W., Argos, P., & Huttner, W. Β. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)80167-3 · Cited by 305 · see citing works
BENEDUM, U., Lamouroux, A., Konecki, D. S., Rosa, P., Hille‐Rehfeld, A., Baeuerle, P. A., Frank, R. W., Lottspeich, F., Mallet, J. J., & Huttner, W. Β. (1987) · The EMBO Journal · doi:10.1002/j.1460-2075.1987.tb02355.x · Cited by 229 · see citing works
Loh, Y. P., Parish, D. C., & Tuteja, R. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39593-5 · Cited by 180 · see citing works
Self-citationChromogranins A, B, and C: Widespread Constituents of Secretory Vesiclesa
Fischer‐Colbrie, R., Hagn, C., & Schober, M. (1987) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1987.tb27189.x · Cited by 177 · see citing works
Iacangelo, A. L., & Eiden, L. E. (1995) · Regulatory Peptides · doi:10.1016/0167-0115(95)00069-n · Cited by 172 · see citing works
Self-citationFunctional Identification and Molecular Cloning of a Human Brain Vesicle Monoamine Transporter
Erickson, J. D., & Eiden, L. E. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb07476.x · Cited by 158 · see citing works
Self-citationRegulated Exocytosis in Chromaffin Cells
Galas, M., Helms, J. B., Vitale, N., Thiersé, D., Aunis, D., & Bader, M. F. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.5.2788 · Cited by 150 · see citing works
Structure and function of the chromogranin A gene. Clues to evolution and tissue-specific expression
Wu, H. J., Rozansky, D. J., Parmer, R. J., Gill, B. M., & O’Connor, D. T. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)98814-9 · Cited by 105 · see citing works
Constitutive and basal secretion from the endocrine cell line, AtT-20.
Matsuuchi, L., & Kelly, R. B. (1991) · The Journal of Cell Biology · doi:10.1083/jcb.112.5.843 · Cited by 94 · see citing works
Gorr, S., Shioi, J., & Cohn, D. V. (1989) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1989.257.2.e247 · Cited by 89 · see citing works
Signal-mediated sorting of neuropeptides and prohormones:Secretory granule biogenesis revisited
Glombik, M. M. (2000) · Biochimie · doi:10.1016/s0300-9084(00)00195-4 · Cited by 84 · see citing works
Fischer‐Colbrie, R., & Schober, M. (1987) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1987.tb13157.x · Cited by 82 · see citing works
Tanner, V., Ploug, T., & Tao-Cheng, J.-H. (1996) · Journal of Histochemistry & Cytochemistry · doi:10.1177/44.12.8985140 · Cited by 80 · see citing works
Self-citationThe Granin Family. Its Role in Sorting and Secretory Granule Formation.
Ozawa, H., & Takata, K. (1995) · Cell Structure and Function · doi:10.1247/csf.20.415 · Cited by 79 · see citing works
Yoo, S. H., & Lewis, M. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.29.17041 · Cited by 68 · see citing works
pH- and Ca2+-induced Conformational Change and Aggregation of Chromogranin B.
Yoo, S. H. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.21.12578 · Cited by 61 · see citing works
Heisler, S., & Reisine, T. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb12757.x · Cited by 58 · see citing works
Iacangelo, A. L., Grimes, M. L., & Eiden, L. E. (1991) · Molecular Endocrinology · doi:10.1210/mend-5-11-1651 · Cited by 53 · see citing works
Self-citationN- and C-terminal Domains Direct Cell Type-specific Sorting of Chromogranin A to Secretory Granules
Cowley, D. J., Moore, Y. R., Darling, D. S., Joyce, P. B. M., & Gorr, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.11.7743 · Cited by 50 · see citing works
Overall Lack of Regulated Secretion in a PC12 Variant Cell Clone
Corradi, N., Borgonovo, B., Clementi, E., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.43.27116 · Cited by 44 · see citing works
Pan-neuronal expression of chromogranin A in rat nervous system
Schäfer, M. K. H., Nöhr, D., Romeo, H. E., et al. (1994) · Peptides · doi:10.1016/0196-9781(94)90012-4 · Cited by 40 · see citing works
Watanabe, T., Banno, T., Jeziorowski, T., et al. (1998) · Endocrinology · doi:10.1210/endo.139.6.6059 · Cited by 37 · see citing works
Aggregation chaperones enhance aggregation and storage of secretory proteins in endocrine cells.
JAIN, R. K., Joyce, P. B. M., & Gorr, S. (2000) · PubMed · doi:10.1074/jbc.m000095200 · Cited by 36 · see citing works
Aggregation Chaperones Enhance Aggregation and Storage of Secretory Proteins in Endocrine Cells
JAIN, R. K., Joyce, P. B. M., & Gorr, S. (2000) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61476-6 · Cited by 29 · see citing works
A PC12 Variant Lacking Regulated Secretory Organelles
Pance, A., Morgan, K., Guest, P. C., et al. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0730021.x · Cited by 25 · see citing works
Transmembrane signals mediating adrenocorticotropin release from mouse anterior pituitary cells
Castro, M. G., Gusovsky, F., & Loh, Y. P. (1989) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(89)90177-9 · Cited by 20 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Miyamoto, S., Duncan, G. E., Marx, C. E., & Lieberman, J. A. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001556 · Cited by 988 · see citing works
Chromogranin A—Biological Function and Clinical Utility in Neuro Endocrine Tumor Disease
Modlin, I. M., Gustafsson, B. I., Moss, S. F., Pavel, M., Tsolakis, A. V., & Kidd, M. (2010) · Annals of Surgical Oncology · doi:10.1245/s10434-010-1006-3 · Cited by 387 · see citing works
Dense-core secretory granule biogenesis
Kim, T., Gondré-Lewis, M. C., Arnaoutova, I., & Loh, Y. P. (2006) · Physiology · doi:10.1152/physiol.00043.2005 · Cited by 203 · see citing works
Self-citationBiogenesis of secretory granules
Borgonovo, B., Ouwendijk, J., & Solimena, M. (2006) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2006.06.010 · Cited by 100 · see citing works
Díaz‐Vera, J., Camacho, M., Machado, J. D., Domínguez, N., Montesinos, M. S., Hernández‐Fernaud, J. R., Luján, R., & Borges, R. (2012) · The FASEB Journal · doi:10.1096/fj.11-181941 · Cited by 55 · see citing works
Pasqua, T., Mahata, S., Bandyopadhyay, G. K., Biswas, A., Perkins, G. A., Sinha-Hikim, A. P., Goldstein, D. S., Eiden, L. E., & Mahata, S. K. (2016) · Cell and Tissue Research · doi:10.1007/s00441-015-2316-3 · Cited by 53 · see citing works
Self-citationIntestinal microbiota modulates adrenomedullary response through Nod1 sensing in chromaffin cells
Xiang, C., Chen, P., Zhang, Q., Li, Y., Pan, Y., Xie, W., Sun, J., & Liu, Z. (2021) · iScience · doi:10.1016/j.isci.2021.102849 · Cited by 15 · see citing works
- Authors
- Kim, T., Tao-Cheng, J.-H., Eiden, L. E., & Loh, Y. P.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Loh, Y.Peng
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2001-08
- Volume
- 106
- Issue
- 4
- Pages
- 499-509
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2069225280
- Cited by
- 414
- References
- 30
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 4 · 2023: 9 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 9 · 2018: 12 · 2017: 17 · 2016: 5 · 2015: 19 · 2014: 13 · 2013: 16 · 2012: 19
- FWCI
- 10.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- chromogranin A, secretory granule biogenesis, regulated secretion, hormone secretion, endocrine cells, neuroendocrine cells, PC12 cells, pituitary cells, antisense RNA knockdown
- MeSH terms
- Animals, Cattle, Chromogranins, Fibroblasts, Immunohistochemistry, Pro-Opiomelanocortin, Transfection, Immunoblotting, RNA, Antisense, PC12 Cells, Secretory Vesicles, Mice, Rats, Chromogranin A
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review