Functional cross talk between ENaC and pendrin.
Functional cross talk between ENaC and pendrin.
复制标题
ENaC 和 pendrin 之间的功能串扰。
DOI：
10.1152/ajprenal.00402.2007
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Kleyman,ThomasR
中科院分区：
文献类型：
--
作者：
Hughey,RebeccaP;Kleyman,ThomasR
上皮Na+通道（ENaC）在醛固酮敏感的远端肾单位中表达，在那里它们充当肾Na+重吸收的最终位点并参与细胞外液体积和血压的调节。ENaC功能获得性突变与高血压相关，而功能丧失性突变与低血压相关。对调节ENaC表达和活性的特征的理解有助于我们理解肾脏在血压调节中的作用。ENaC结构，组装和成熟。ENaC由内质网（ER）内的三个高度同源的亚基组装成四聚体结构（α2β1γ1），尽管也提出了更高阶的化学计量（3，12，21）。考虑到最终在到达细胞表面的通道中仅发现有限部分的新合成亚基，组装似乎是低效的（16，26）。每个亚基都具有细胞内氨基和羧基末端、两个跨膜结构域和一个大的细胞外环（ECL），其中有许多N-连接糖基化位点（2，3）。离开ER的未成熟通道随后通过N-连接聚糖的重塑和ECL的蛋白水解裂解进行加工（5，6）。
Epithelial Na+ channels (ENaC) are expressed in the aldosterone-sensitive distal nephron, where they serve as the final site of renal Na+ reabsorption and participate in the regulation of extracellular fluid volume and blood pressure. ENaC gain-of-function mutations are associated with hypertension, whereas loss-of-function mutations are associated with hypotension. Appreciation of the features that regulate ENaC expression and activity contributes to our understanding of the role of the kidney in the regulation of blood pressure.ENaC structure, assembly and maturation. ENaC is assembled into a tetrameric structure (α2β1γ1) from three highly homologous subunits within the endoplasmic reticulum (ER), although higher ordered stoichiometries have also been proposed (3, 12, 21). The assembly appears to be inefficient given that only a limited fraction of newly synthesized subunits are eventually found in channels that reach the cell surface (16, 26). Each subunit exhibits intracellular aminoand carboxyl-termini, two transmembrane domains and a large extracellular loop (ECL) with numerous sites for N-linked glycosylation (2, 3). Immature channels that exit the ER are subsequently processed by remodeling of the N-linked glycans and proteolytic cleavage of the ECLs (5, 6).