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Chromogranin B forms the chloride channel required for regulated secretion
Author(s) -
Jiang QiuXing,
Yadav Gaya,
Zheng Hui,
Yang Qing
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1224.40
Subject(s) - secretory vesicle , secretion , chromogranin a , biogenesis , microbiology and biotechnology , chemistry , vesicle , chloride channel , biophysics , enteroendocrine cell , chloride , biochemistry , exocytosis , biology , membrane , endocrine system , hormone , immunology , immunohistochemistry , organic chemistry , gene
Endocrine cells use regulated secretory pathway to process and package small proteins and organic molecules into granular secretory vesicles that are released in a finely controlled manner ( 1–3 ). Acidification of secretory granules is essential for cargo maturation inside them. Vesicular H + ‐ATPase pumps protons into secretory granules( 4 ). But identity of the accompanying anion channel to neutralize charge accumulation in granules remains uncertain ( 5–7 ). We discover that chromogranin B (CHGB) is both sufficient and necessary to serve the highly selective anion conductance required for acidification and cargo maturation in insulin‐secreting cells. We find that CHGB uses different domains for channel formation and granular biogenesis, allowing the separation of these two essential functions. Our results establish that CHGBs constitute a new type of pH and calcium‐regulated chloride channel specific to regulated secretion. Support or Funding Information NIH R01GM093271Welch Foundation I‐1684CPRIT RP120474AHA 12IRG9400019NIH R01GM088745