Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis

Cell. 2001 Aug 24;106(4):499-509. doi: 10.1016/s0092-8674(01)00459-7.


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.

MeSH terms

  • Animals
  • Cattle
  • Chromogranin A
  • Chromogranins / genetics
  • Chromogranins / metabolism*
  • Fibroblasts / metabolism
  • Immunoblotting
  • Immunohistochemistry
  • Mice
  • PC12 Cells
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / metabolism
  • RNA, Antisense / metabolism
  • Rats
  • Secretory Vesicles / metabolism*
  • Transfection


  • Chromogranin A
  • Chromogranins
  • RNA, Antisense
  • chromogranin A, mouse
  • chromogranin A, rat
  • Pro-Opiomelanocortin