| First Author | Rahman N | Year | 2016 |
| Journal | J Gen Physiol | Volume | 148 |
| Issue | 4 | Pages | 325-39 |
| PubMed ID | 27670898 | Mgi Jnum | J:326426 |
| Mgi Id | MGI:6835369 | Doi | 10.1085/jgp.201611606 |
| Citation | Rahman N, et al. (2016) Soluble adenylyl cyclase is essential for proper lysosomal acidification. J Gen Physiol 148(4):325-39 |
| abstractText | 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 serves 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. |
