Soluble adenylyl cyclase is essential for proper lysosomal acidification

Nawreen Rahman, Lavoisier Ramos-Espiritu, Teresa A. Milner, Jochen Buck, Lonny R. Levin
2016 The Journal of General Physiology  
Lysosomes, the degradative organelles of the endocytic and autophagic pathways, function at an acidic pH. Lysosomes are acidified by the proton-pumping vacuolar ATPase (V-ATPase), but the molecular processes that set the organelle's pH are not completely understood. In particular, pH-sensitive signaling enzymes that can regulate lysosomal acidification in steady-state physiological conditions have yet to be identified. Soluble adenylyl cyclase (sAC) is a widely expressed source of cAMP that
more » ... es as a physiological pH sensor in cells. For example, in proton-secreting epithelial cells, sAC is responsible for pH-dependent translocation of V-ATPase to the luminal surface. Here we show genetically and pharmacologically that sAC is also essential for lysosomal acidification. In the absence of sAC, V-ATPase does not properly localize to lysosomes, lysosomes fail to fully acidify, lysosomal degradative capacity is diminished, and autophagolysosomes accumulate.
doi:10.1085/jgp.201611606 pmid:27670898 pmcid:PMC5037342 fatcat:7d52v7736vdapblebmlqr7lrba