AUTHOR=Chang Jung-Chin , Oude Elferink Ronald TITLE=Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation JOURNAL=Frontiers in Physiology VOLUME=Volume 5 - 2014 YEAR=2014 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2014.00042 DOI=10.3389/fphys.2014.00042 ISSN=1664-042X 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.