The Calcineurin Homologous Protein-1 Increases Na+/H+-Exchanger 3 Trafficking via Ezrin Phosphorylation
The Calcineurin Homologous Protein-1 Increases Na+/H+-Exchanger 3 Trafficking via Ezrin Phosphorylation
复制标题
DOI：
10.1681/asn.2008121255
复制
发表时间：
2009-08-01
影响因子：
13.6
通讯作者：
Moe, Orson W.
中科院分区：
文献类型：
--
作者：
Di Sole, Francesca;Babich, Victor;Moe, Orson W.
Na+/H+-交换剂3 （NHE3）是调节肾和肠上皮内Na+转运的必要物质。虽然细胞表面丰度的变化控制着NHE3的功能，但调控NHE3表面表达的分子信号尚未明确。我们发现，负鼠肾细胞中钙调神经磷酸酶同源蛋白-1 （CHP1）的过表达增加了NHE3转运活性、表面蛋白丰度和ezrin磷酸化。小干扰RNA敲低CHP1具有相反的效果。野生型ezrin的过表达增加了NHE3转运活性和表面蛋白丰度，证实了NHE3在ezrin的下游。假磷酸化ezrin的表达增强了这些作用，而不能磷酸化的ezrin变体的表达阻止了对NHE3的下游作用。此外，CHP1的敲低逆转了野生型ezrin对NHE3的激活，而假磷酸化ezrin则没有。综上所述，这些结果表明CHP1以依赖于ezrin磷酸化的方式增加NHE3丰度和组成功能。
The Na+/H+-exchanger 3 (NHE3) is essential for regulation of Na+ transport in the renal and intestinal epithelium. Although changes in cell surface abundance control NHE3 function, the molecular signals that regulate NHE3 surface expression are not well defined. We found that overexpression of the calcineurin homologous protein-1 (CHP1) in opossum kidney cells increased NHE3 transport activity, surface protein abundance, and ezrin phosphorylation. CHP1 knockdown by small interfering RNA had the opposite effects. Overexpression of wild-type ezrin increased both NHE3 transport activity and surface protein abundance, confirming that NHE3 is downstream of ezrin. Expression of a pseudophosphorylated ezrin enhanced these effects, whereas expression of an ezrin variant that could not be phosphorylated prevented the downstream effects on NHE3. Furthermore, CHP1 knockdown reversed the activation of NHE3 by wild-type ezrin but not by the pseudophosphorylated ezrin. Taken together, these results demonstrate that CHP1 increases NHE3 abundance and constitutive function in a manner dependent on ezrin phosphorylation.