Division of Nephrology, Department of Medicine, University of California-San Francisco, CA 94143, USA.
Mol Cell Endocrinol. 2012 Mar 24;350(2):242-7. doi: 10.1016/j.mce.2011.11.003. Epub 2011 Nov 12.
The mineralocorticoid aldosterone is indispensable for the control of blood pressure and fluid volume in mammals. It acts in large part to increase the abundance and activity of the epithelial Na(+) channel (ENaC), which mediates apical Na(+) entry in the distal parts of the kidney tubules. Aldosterone acts through the mineralocorticoid receptor to alter the transcription of specific genes, including SGK1 and GILZ1. Recent evidence suggests that these key aldosterone-regulated factors function within a unique multi-protein ENaC-regulatory-complex that governs the net cell surface expression and activity of the channel. Another aldosterone-induced protein, CNK3 (connector enhancer of kinase suppressor of Ras 3), also stimulates ENaC and has all of the features of a scaffolding protein. With these observations in mind, we discuss the possibility that CNK3 coordinates the dynamic assembly of the ENaC-regulatory-complex, and promotes context-appropriate aldosterone signal transduction in the regulation of epithelial Na(+) transport.
醛固酮是哺乳动物血压和血容量控制所必需的。它在很大程度上通过增加上皮钠通道 (ENaC) 的丰度和活性来发挥作用，ENaC 介导肾脏远曲小管顶端的 Na+内流。醛固酮通过盐皮质激素受体作用于特定基因的转录，包括 SGK1 和 GILZ1。最近的证据表明，这些关键的醛固酮调节因子在一个独特的多蛋白 ENaC 调节复合物内发挥作用，该复合物控制通道的净细胞表面表达和活性。另一种醛固酮诱导的蛋白，CNK3（连接增强激酶抑制剂 Ras3），也刺激 ENaC，并且具有支架蛋白的所有特征。考虑到这些观察结果，我们讨论了 CNK3 是否协调 ENaC 调节复合物的动态组装，并在调节上皮 Na+转运中促进适当的醛固酮信号转导。
