Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis.
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.
Kim
T
T
Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Tao-Cheng
J H
JH
Eiden
L E
LE
Loh
Y P
YP
D000818:Animals; D002417:Cattle; D053379:Chromogranin A; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D016716:PC12 Cells; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D016372:RNA, Antisense / Q000378:metabolism; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D014162:Transfection
D053379:Chromogranin A; D002864:Chromogranins; D016372:RNA, Antisense; C506155:chromogranin A, mouse; C506153:chromogranin A, rat; D011333:Pro-Opiomelanocortin