Gastric Acid Secretion from Parietal Cells Is Mediated by a Ca²⁺ Efflux Channel in the Tubulovesicle.

ABSTRACT: Gastric acid secretion by parietal cells requires trafficking and exocytosis of H/K-ATPase-rich tubulovesicles (TVs) toward apical membranes in response to histamine stimulation via cyclic AMP elevation. Here, we found that TRPML1 (ML1), a protein that is mutated in type IV mucolipidosis (ML-IV), is a tubulovesicular channel essential for TV exocytosis and acid secretion. Whereas ML-IV patients are reportedly achlorhydric, transgenic overexpression of ML1 in mouse parietal cells induced constitutive acid secretion. Gastric acid secretion was blocked and stimulated by ML1 inhibitors and agonists, respectively. Organelle-targeted Ca²⁺ imaging and direct patch-clamping of apical vacuolar membranes revealed that ML1 mediates a PKA-activated conductance on TV membranes that is requir

SUBMITTER: Sahoo N 

PROVIDER: S-EPMC5497767 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature