Journal of Biological Chemistry
Volume 279, Issue 7, 13 February 2004, Pages 5429-5434
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Membrane Transport, Structure, Function, and Biogenesis
Identification of Murr1 as a Regulator of the Human δ Epithelial Sodium Channel*

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The human δ epithelial sodium channel (δENaC) subunit is related to the α-, β-, and γENaC subunits that control salt homeostasis. δENaC forms an amiloride-sensitive Na+ channel with the β and γ subunits. However, the in vivo function of δENaC is not known. To gain insight into the function of δENaC, a yeast two-hybrid screen of a human brain cDNA library was carried out using the C- and N-terminal domains of δENaC. A novel δENaC-interacting protein called Murr1 (mouse U2af1-rs1 region) was isolated in the C-terminal domain screen. Murr1 is a 21-kDa protein mutated in Bedlington terriers suffering from copper toxicosis. The interaction of Murr1 and δENaC was confirmed by glutathione S-transferase pulldown assay and coimmunoprecipitation. To test the functional significance of the interaction, Murr1 was coexpressed with δβγENaC in Xenopus oocytes. Murr1 inhibited amiloride-sensitive sodium current in a dose-dependent manner. In addition, deletion of the last 59 amino acids of δENaC abolished the inhibition. Murr1 also bound to the β- and γENaC subunits and inhibited αβγENaC sodium current. Therefore, these results suggest that Murr1 is a novel regulator of ENaC.

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This work was supported by a grant from the Marsden Fund of New Zealand. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.