CHROMOGRANIN-B (SECRETOGRANIN-I) PROMOTES SORTING TO THE REGULATED SECRETORY PATHWAY OF PROCESSING INTERMEDIATES DERIVED FROM A PEPTIDE-HORMONE PRECURSOR

Chromogranin B (CgB, secretogranin I) is a widespread constituent of n euroendocrine secretory granules whose function is unknown. To determi ne whether CgB affects the sorting of peptide hormone and neuropeptide precursors to secretory granules, pie overexpressed CgB in AtT-20 cel ls, which exhibit an only moderate capacity to sort proopiomelanocorti n and proteolytic fragments derived therefrom. In mock-transfected AtT -20 cells, a substantial proportion of newly synthesized proopiomelano cortin and its two primary proteolytic products generated in the trans -Golgi network, the N-terminal 23-kDa fragment containing adrenocortic otropin and the C-terminal beta-lipotropin fragment, was secreted via the constitutive pathway. Two- to three-fold overexpression of CgB mar kedly reduced the constitutive secretion of the 23-kDa fragment, but n ot beta-lipotropin and tripled the amount of adrenocorticotropin gener ated and stored in secretory granules. Our results indicate the existe nce of neuroendocrine specific helper proteins which promote the sorti ng from the trans-Golgi network to secretory granules of certain proce ssing intermediates derived from peptide hormone and neuropeptide prec ursors and demonstrate that CgB functions as such.