Work

Soluble adenylyl cyclase is essential for proper lysosomal acidification

Year: 2016

Type: article

Abstract: 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.

Source: The Journal of General Physiology

DOI: 10.1085/jgp.201611606

Authors: Nawreen Rahman, Lavoisier Ramos-Espiritu, Teresa A. Milner, Jochen Buck, Lonny R. Levin

Institutions: Weill Cornell Medicine, Rockefeller University

Language: English

Topic: Calcium signaling and nucleotide metabolism

Subfield: Physiology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke