Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation.
Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation.
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DOI:
10.3389/fphys.2014.00042
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发表时间:
2014
影响因子:
4
通讯作者:
Oude-Elferink RP
中科院分区:
文献类型:
--
作者:
Chang JC;Oude-Elferink RP
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.
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