Normal mucus formation requires cAMP‐dependent HCO3− secretion and Ca2+‐mediated mucin exocytosis

•  HCO3− is required for gel‐forming mucins to form normal mucus, but how? •  Two apparently separate signalling pathways are activated concurrently to bring mucus formation to completion: a Ca2+‐mediated pathway mainly directs goblet cell exocytosis, and an independent cAMP‐mediated pathway stimulates HCO3− secretion to help discharge exocytosed mucus. •  cAMP‐dependent HCO3− secretion fails, disrupting the normal formation and discharge of mucins in cystic fibrosis (CF) leading to pathologically viscous and tenacious mucus in affected organs. •  This work advances our understanding of the role of cAMP (CFTR)‐dependent HCO3− secretion in forming normal mucus and underscores a new importance of addressing the defect in HCO3− secretion as a critical new therapeutic target in CF.

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