Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/53593
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Type: Journal article
Title: Regulation of the voltage-gated K⁺ channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1
Other Titles: Regulation of the voltage-gated K+ channels KCNQ2/3 and KCNQ3/5 by serum- and glucocorticoid-regulated kinase-1
Author: Schuetz, F.
Kumar, S.
Poronnik, P.
Adams, D.
Citation: American Journal of Physiology-Cell Physiology, 2008; 295(1):C73-C80
Publisher: Amer Physiological Soc
Issue Date: 2008
ISSN: 0363-6143
1522-1563
Statement of
Responsibility: 
Friderike Schuetz, Sharad Kumar, Philip Poronnik and David J. Adams
Abstract: The voltage-gated KCNQ2/3 and KCNQ3/5 K(+) channels regulate neuronal excitability. We recently showed that KCNQ2/3 and KCNQ3/5 channels are regulated by the ubiquitin ligase Nedd4-2. Serum- and glucocorticoid-regulated kinase-1 (SGK-1) plays an important role in regulation of epithelial ion transport. SGK-1 phosphorylation of Nedd4-2 decreases the ability of Nedd4-2 to ubiquitinate the epithelial Na(+) channel, which increases the abundance of channel protein in the cell membrane. In this study, we investigated the mechanism(s) of SGK-1 regulation of M-type KCNQ channels expressed in Xenopus oocytes. SGK-1 significantly upregulated the K(+) current amplitudes of KCNQ2/3 and KCNQ3/5 channels approximately 1.4- and approximately 1.7-fold, respectively, whereas the kinase-inactive SGK-1 mutant had no effect. The cell surface levels of KCNQ2-hemagglutinin/3 were also increased by SGK-1. Deletion of the KCNQ3 channel COOH terminus in the presence of SGK-1 did not affect the K(+) current amplitude of KCNQ2/3/5-mediated currents. Coexpression of Nedd4-2 and SGK-1 with KCNQ2/3 or KCNQ3/5 channels did not significantly alter K(+) current amplitudes. Only the Nedd4-2 mutant (S448A)Nedd4-2 exhibited a significant downregulation of the KCNQ2/3/5 K(+) current amplitudes. Taken together, these results demonstrate a potential mechanism for regulation of KCNQ2/3 and KCNQ3/5 channels by SGK-1 regulation of the activity of the ubiquitin ligase Nedd4-2.
Keywords: KCNQ channel; M current; potassium channel; ubiquitin ligase; Xenopus oocyte
RMID: 0020081398
DOI: 10.1152/ajpcell.00146.2008
Appears in Collections:Medicine publications

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