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
Oude-Elferink RP
中科院分区:
医学2区
文献类型:
--
作者:
Chang JC;Oude-Elferink RP

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进化上保守的可溶性腺苷酸环化酶(sAC, adcy10)最近被发现是细胞质和细胞核中cAMP的独特来源。它的活性由碳酸氢盐调节,由钙调节。因此,sAC与碳酸酐酶(CA)一起构成HCO−3/CO−2/pH传感器。在收集管的α嵌入细胞和附睾的透明细胞中,sAC的表达水平显著,并以pka依赖的方式通过液泡H+- atp酶(VHA)的顶端募集参与pH稳态。除了维持pH稳态外,sAC还参与代谢调节,如通过碳酸氢盐/二氧化碳传感将Krebs循环偶联到氧化磷酸化。此外,sAC还调节CFTR通道,在调节屏障功能和细胞凋亡中发挥重要作用。这些观察结果表明,sAC通过碳酸氢盐感应,在维持细胞对抗微环境波动的稳态状态中起着重要作用。
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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