The V-ATPase membrane domain is a sensor of granular pH that controls the exocytotic machinery

Abstract

The V0 membrane domain of the V-ATPase reversibly dissociates from V1 at acidic intragranular pH and is necessary for normal exocytosis and synaptic transmission.

Defective goblet cell exocytosis contributes to murine cystic fibrosis–associated intestinal disease

“…More consistent with our observations, it is known that an alkaline granule pH slows or even inhibits exocytosis in secretory cells. In chromaffin granule membranes, disassociation of the multimeric V0 subunit from the V1 subunit of the V-ATPase is an inverse linear function of intragranular pH, and the disassociated V0 subunit is important to formation of the fusion pore (71). An alkaline granule pH also reduces granule Ca 2+ signaling by mucin granules, which may delay exocytosis and diminish feedback to the goblet cell of the exocytotic event (25).…”

Recent Insights into the Structure, Regulation, and Function of the V-ATPases

“…Similarly, an inactive mutant of the a1 subunit is able to restore synaptic vesicle release in a Drosophila strain in which a1 has been disrupted, suggesting an acidification-independent role of V 0 in synaptic vesicle fusion [105]. In fact, V 0 has been suggested to serve as a pH sensor that helps control vesicle fusion [106]. By contrast, whereas an inactive mutant of the yeast a subunit isoform Vphlp is not able to rescue homotypic vacuole fusion in a Vph1p-null yeast strain, introduction of a proton pumping pyrophosphatase from plant at least partially restored fusion, suggesting vacuolar acidification is the primary role of the V-ATPase in this system [107].…”

Disruption of the vacuolar-type H+-ATPase complex in liver causes MTORC1-independent accumulation of autophagic vacuoles and lysosomes

“…To this end, we treated control cells with BafA1, which blocks proton pump activity and favors the disassembly of the complex, [36][37][38] or with saliphenylhalamide A, which inactivates and promotes assembly of the complex. 32,39 We performed experiments in the presence of a constant concentration of either of these drugs analyzing MTORC1 reactivation at different times after re-addition of amino acids (Fig.…”