The A-kinase anchoring protein 15 regulates feedback inhibition of the epithelial Na+ channel
The A-kinase anchoring protein 15 regulates feedback inhibition of the epithelial Na+ channel
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DOI：
10.1096/fj.06-6046com
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发表时间：
2007-04-01
期刊：
影响因子：
4.8
通讯作者：
Awayda，Mouhamed S.
中科院分区：
文献类型：
--
作者：
Bengrine，Abderrahmane;Li，Jinqing;Awayda，Mouhamed S.
Protein kinase A anchoring proteins or AKAPs regulate the activity of many ion channels. Protein kinase A (PKA) is a well‐recognized target of AKAPs, with other kinases now emerging as additional targets. We examined the roles of epithelial‐expressed AKAPs in regulating the epithelial Na+channel (ENaC). Experiments used heterologous expression with AKAP15, AKAP‐KL, and AKAP79 inXenopusoo‐cytes. Experiments were carried out under high and low Na+conditions, as Na+loading is known to affect the baseline activity of ENaC in a PKC‐dependent mechanism. ENaC activity was unaffected by AKAP79 and AKAP‐KL expression. However, oocytes coexpressing AKAP15 exhibited an 80% and 91% reduction in the amiloride‐sensitive, whole‐cell conductance in high and low Na+conditions, respectively. The reduced channel activity was unaffected by PKA activation or inhibition, indicating a PKA‐independent mechanism. Expression with a membrane‐targeting domain, mutant form of AKAP15 (AKAP15m) prevented the decrease of ENaC activity, but only under low Na+conditions. In high sodium conditions, coexpression with AKAP15m led to an increase of ENaC activity to levels similar to those observed under low Na+. These results indicate that membrane‐associated AKAP15 reduces ENaC activity whereas the cytoplasmically associated one may participate in the channel's feedback inhibition by intracellular Na+, a process known to involve PKC. This hypothesis was further confirmed in coexpression experiments, which demonstrated functional and physical interaction between AKAP15 and PKCα. We propose that AKAP15 regulates ENaCviaa novel PKA‐indepen‐dent pathway.—Bengrine, A., Li, J., Awayda, M. S. The A‐kinase anchoring protein 15 regulates feedback inhibition of the epithelial Na+channel.FASEB J.21, 1189–1201 (2007)
