Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel
Functional interaction of COMMD3 and COMMD9 with the epithelial sodium channel
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DOI：
10.1152/ajprenal.00158.2013
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发表时间：
2013-07-01
影响因子：
4.2
通讯作者：
McDonald, Fiona J.
中科院分区：
文献类型：
--
作者：
Liu, Yong Feng;Swart, Marianne;McDonald, Fiona J.
上皮钠通道（ENaC）在控制Na+稳态、细胞外液容量和血压方面起着重要作用。铜代谢Murr1结构域含蛋白1 （COMMD1）与ENaC相互作用并下调ENaC。COMMD1属于COMMD1-10组成的COMMD族，所有COMMD族成员共用一个c端COMM域。在这里，我们报道COMMD2-10也与ENaC相互作用，并选择COMMD3和COMMD9进行进一步研究。COMMD3或COMMD9显著降低了表达ENaC的哺乳动物上皮中阿米罗利敏感电流，COMMD3或COMMD9显著降低了细胞表面ENaC的表达。当COMMD1被敲除时，COMMD3和COMMD9仍保持其减小电流的能力。COMMD3和COMMD9在肾脏中广泛表达，并与ENaC在肾集管细胞中共定位。这些数据表明COMMD3和COMMD9可能是ENaC的内源性调节剂，通过改变ENaC细胞表面表达来调节Na+转运。
The epithelial sodium channel (ENaC) plays an important role in controlling Na+ homeostasis, extracellular fluid volume, and blood pressure. Copper metabolism Murr1 domain-containing protein 1 (COMMD1) interacts with ENaC and downregulates ENaC. COMMD1 belongs to the COMMD family consisting of COMMD1-10, and all COMMD family members share a C-terminal COMM domain. Here, we report that COMMD2-10 also interacts with ENaC, and COMMD3 and COMMD9 were selected for further study. Amiloride-sensitive current in mammalian epithelia expressing ENaC was significantly reduced by COMMD3 or COMMD9, and ENaC expression at the cell surface was significantly decreased in the presence of COMMD3 or COMMD9. COMMD3 and COMMD9 retained their ability to reduce current when COMMD1 was knocked down. COMMD3 and COMMD9 were widely expressed in kidney and were colocalized with ENaC in renal collecting duct cells. These data suggest that COMMD3 and COMMD9 may be endogenous regulators of ENaC to regulate Na+ transport through altering ENaC cell surface expression.