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- Title
Chromogranin B: intra- and extra-cellular mechanisms to regulate catecholamine storage and release, in catecholaminergic cells and organisms.
- Authors
Zhang, Kuixing; Biswas, Nilima; Gayen, Jiaur R.; Miramontes‐Gonzalez, Jose Pablo; Hightower, C. Makena; Mustapic, Maja; Mahata, Manjula; Huang, Chun‐Teng; Hook, Vivian Y.; Mahata, Sushil K.; Vaingankar, Sucheta; O'Connor, Daniel T.
- Abstract
Chromogranin B ( CHGB) is the major matrix protein in human catecholamine storage vesicles. CHGB genetic variation alters catecholamine secretion and blood pressure. Here, effective Chgb protein under-expression was achieved by si RNA in PC12 cells, resulting in ~ 48% fewer secretory granules on electron microscopy, diminished capacity for catecholamine uptake (by ~ 79%), and a ~ 73% decline in stores available for nicotinic cholinergic-stimulated secretion. In vivo, loss of Chgb in knockout mice resulted in a ~ 35% decline in chromaffin granule abundance and ~ 44% decline in granule diameter, accompanied by unregulated catecholamine release into plasma. Over-expression of CHGB was achieved by transduction of a CHGB-expressing lentivirus, resulting in ~ 127% elevation in CHGB protein, with ~ 122% greater abundance of secretory granules, but only ~ 14% increased uptake of catecholamines, and no effect on nicotinic-triggered secretion. Human CHGB protein and its proteolytic fragments inhibited nicotinic-stimulated catecholamine release by ~ 72%. One conserved-region CHGB peptide inhibited nicotinic-triggered secretion by up to ~ 41%, with partial blockade of cationic signal transduction. We conclude that bi-directional quantitative derangements in CHGB abundance result in profound changes in vesicular storage and release of catecholamines. When processed and released extra-cellularly, CHGB proteolytic fragments exert a feedback effect to inhibit catecholamine secretion, especially during nicotinic cholinergic stimulation.
- Subjects
CHROMOGRANINS; BIOLOGICAL transport; CELLULAR mechanics; MICROBIAL genetics; CHROMAFFIN cells
- Publication
Journal of Neurochemistry, 2014, Vol 129, Issue 1, p48
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.12527