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Relative Contribution Of Nedd4 And Nedd4-2 To Enac Regulation In Epithelia Determined By Rna Interference., Peter Snyder, Jennifer Steines, Diane Olson
Relative Contribution Of Nedd4 And Nedd4-2 To Enac Regulation In Epithelia Determined By Rna Interference., Peter Snyder, Jennifer Steines, Diane Olson
Jennifer C. Steines Wagemester
Epithelial Na+ transport is regulated in large part by mechanisms that control expression of the epithelial Na+ channel (ENaC) at the cell surface. Nedd4 and Nedd4-2 are candidates to control ENaC surface expression, but it is not known which of these proteins contributes to ENaC regulation in epithelia. To address this question, we used RNA interference to selectively reduce expression of Nedd4 or Nedd4-2. We found that endogenous Nedd4-2, but not Nedd4, negatively regulates ENaC in two epithelial cell lines (Fischer rat thyroid and H441); small interfering RNA (siRNA) against Nedd4-2 increased amiloride-sensitive Na+ current (compared with control siRNA), but …
Camp And Serum And Glucocorticoid-Inducible Kinase (Sgk) Regulate The Epithelial Na(+) Channel Through Convergent Phosphorylation Of Nedd4-2., Peter Snyder, Diane Olson, Rajesh Kabra, Ruifeng Zhou, Jennifer Steines
Camp And Serum And Glucocorticoid-Inducible Kinase (Sgk) Regulate The Epithelial Na(+) Channel Through Convergent Phosphorylation Of Nedd4-2., Peter Snyder, Diane Olson, Rajesh Kabra, Ruifeng Zhou, Jennifer Steines
Jennifer C. Steines Wagemester
The epithelial Na(+) channel (ENaC) functions as a pathway for epithelial Na(+) transport, contributing to Na(+) homeostasis and blood pressure control. Vasopressin increases ENaC expression at the cell surface through a pathway that includes cAMP and cAMP-dependent protein kinase (PKA), but the mechanisms that link PKA to ENaC are unknown. Here we found that cAMP regulates Na(+) transport in part by inhibiting the function of Nedd4-2, an E3 ubiquitin-protein ligase that targets ENaC for degradation. Consistent with this model, we found that cAMP inhibited Nedd4-2 by decreasing its binding to ENaC. Moreover, decreased Nedd4-2 expression (RNA interference) or overexpression of …