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

被引：348

作者：

Kim, T

Tao-Cheng, JH

Eiden, LE

Loh, YP ^{[1
]}

机构：

[1] NICHHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA

[2] NINDS, EM Facil, Bethesda, MD 20892 USA

[3] NIMH, Lab Cellular & Mol Regulat, Mol Neurosci Sect, Bethesda, MD 20892 USA

来源：

CELL | 2001年 / 106卷 / 04期

关键词：

D O I：

10.1016/S0092-8674(01)00459-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：499 / 509

页数：11

共 30 条

[1] THE PRIMARY STRUCTURE OF HUMAN SECRETOGRANIN-I (CHROMOGRANIN-B) - COMPARISON WITH CHROMOGRANIN-A REVEALS HOMOLOGOUS TERMINAL DOMAINS AND A LARGE INTERVENING VARIABLE REGION [J].