title: Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation.
abstract: The evolutionarily conserved soluble adenylyl cyclase (sAC, adcy10) was recently identified as a unique source of cAMP in the cytoplasm and the nucleus. Its activity is regulated by bicarbonate and fine-tuned by calcium. As such, and in conjunction with carbonic anhydrase (CA), sAC constitutes an HCO(-) 3/CO(-) 2/pH sensor. In both alpha-intercalated cells of the collecting duct and the clear cells of the epididymis, sAC is expressed at significant level and involved in pH homeostasis via apical recruitment of vacuolar H(+)-ATPase (VHA) in a PKA-dependent manner. In addition to maintenance of pH homeostasis, sAC is also involved in metabolic regulation such as coupling of Krebs cycle to oxidative phosphorylation via bicarbonate/CO2 sensing. Additionally, sAC also regulates CFTR channel and plays an important role in regulation of barrier function and apoptosis. These observations suggest that sAC, via bicarbonate-sensing, plays an important role in maintaining homeostatic status of cells against fluctuations in their microenvironment.
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Jung-Chin
authors.initials: JC
authors.lastname: Chang
authors.affiliation: Tytgat Institute for Liver and Intestinal Research, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
authors.forename: Ronald P J
authors.initials: RP
authors.lastname: Oude-Elferink
keywords: apoptosis; barrier function; carbonic anhydrase; pH regulation; protein kinase A; soluble adenylyl cyclase; vacuolar-ATPase