Soluble adenylyl cyclase is essential for proper lysosomal acidification. Academic Article uri icon

Overview

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.

publication date

  • October 1, 2016

Research

keywords

  • Adenylyl Cyclases
  • Fibroblasts

Identity

PubMed Central ID

  • PMC5037342

Scopus Document Identifier

  • 84991491234

Digital Object Identifier (DOI)

  • 10.1247/csf.23.33

PubMed ID

  • 27670898

Additional Document Info

volume

  • 148

issue

  • 4