Cofilin participates in regulating alpha-epithelial sodium channel by interaction with 14-3-3 isoforms.
Cofilin participates in regulating alpha-epithelial sodium channel by interaction with 14-3-3 isoforms.
复制标题
Cofilin 通过与 14-3-3 异构体相互作用参与调节 α-上皮钠通道
DOI：
10.7555/jbr.34.20190155
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发表时间：
2020-07-30
影响因子：
2.3
通讯作者：
Liang X
中科院分区：
文献类型：
--
作者：
Bukhari AA;Zhang X;Li M;Zhao A;Dong H;Liang X
肾上皮钠通道（renalepithelialsodiumchannel，ENaC）在维持体内平衡和钠吸收中起着至关重要的作用。虽然胰岛素参与控制钠转运通过肾上皮，但其潜在的分子机制仍不清楚。在本研究中，我们发现胰岛素增加了小鼠皮质集合管（mpkCCDc 14）细胞α-上皮钠通道（α-ENaC）的表达和功能，以及cofilin的磷酸化，cofilin是一个肌动蛋白结合蛋白家族，其分解肌动蛋白丝。野生型（WT）cofilin及其组成型磷酸化形式（S3 D），而不是其组成型非磷酸化形式（S3 A），有助于α-ENaC表达的升高。14-3-3ε、β或γ的过表达增加了α-ENaC和cofilin磷酸化的表达，这通过敲低14-3-3ε、β或γ而减弱。此外，发现胰岛素增加了cofilin和14-3-3同种型之间的相互作用，这表明14-3-3同种型与cofilin相关。LIMK 1/SSH 1通路参与胰岛素对cofilin和α-ENaC表达的调控。本研究结果表明，cofilin通过与14-3-3亚型相互作用参与α-ENaC的调节。
Renal epithelial sodium channel (ENaC) plays a crucial role in maintaining homeostasis and sodium absorption. While insulin participates in controlling sodium transport across the renal epithelium, the underlying molecular mechanism remain unclear. In this study, we found that insulin increased the expression and function of alpha-epithelial sodium channel (α-ENaC) as well as phosphorylation of cofilin, a family of actin-binding proteins which disassembles actin filaments, in mouse cortical collecting duct (mpkCCDc14) cells. The wild-type (WT) cofilin and its constitutively phosphorylated form (S3D), but not its constitutively non-phosphorylable form (S3A), contributed to the elevated expression on α-ENaC. Overexpression of 14-3-3ε, β, or γ increased the expression of α-ENaC and cofilin phosphorylation, which was blunted by knockdown of 14-3-3ε, β, or γ. Moreover, it was found that insulin increased the interaction between cofilin and 14-3-3 isoforms, which indicated relevance of 14-3-3 isoforms with cofilin. Furthermore, LIMK1/SSH1 pathway was involved in regulation of cofilin and α-ENaC expression by insulin. The results from this work indicate that cofilin participates in the regulation of α-ENaC by interaction with 14-3-3 isoforms.