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Interactions between β-Catenin and the HSlo Potassium Channel Regulates HSlo Surface Expression

Authors
Journal
PLoS ONE
1932-6203
Publisher
Public Library of Science
Publication Date
Volume
6
Issue
12
Identifiers
DOI: 10.1371/journal.pone.0028264
Keywords
  • Research Article
  • Biology
  • Molecular Cell Biology
  • Signal Transduction
  • Signaling In Cellular Processes
  • Beta-Catenin Signaling
  • Signaling Pathways
  • Catenin Signal Transduction
  • Membranes And Sorting
  • Neuroscience
  • Cellular Neuroscience
  • Ion Channels
  • Sensory Systems
  • Auditory System
Disciplines
  • Biology
  • Medicine

Abstract

Background The large conductance calcium-activated potassium channel alpha-subunit (Slo) is widely distributed throughout the body and plays an important role in a number of diseases. Prior work has shown that Slo, through its S10 region, interacts with β-catenin, a key component of the cytoskeleton framework and the Wnt signaling pathway. However, the physiological significance of this interaction was not clear. Methodology/Principal Findings Using a combination of proteomic and cell biology tools we show the existence of additional multiple binding sites in Slo, and explore in detail β-catenin interactions with the S10 region. We demonstrate that deletion of this region reduces Slo surface expression in HEK cells, which indicates that interaction with beta-catenin is important for Slo surface expression. This is confirmed by reduced expression of Slo in HEK cells and chicken (Gallus gallus domesticus leghorn white) hair cells treated with siRNA to β-catenin. HSlo reciprocally co-immunoprecipitates with β-catenin, indicating a stable binding between these two proteins, with the S10 deletion mutant having reduced binding with β-catenin. We also observed that mutations of the two putative GSK phosphorylation sites within the S10 region affect both the surface expression of Slo and the channel's voltage and calcium sensitivities. Interestingly, expression of exogenous Slo in HEK cells inhibits β-catenin-dependent canonical Wnt signaling. Conclusions and Significance These studies identify for the first time a central role for β-catenin in mediating Slo surface expression. Additionally we show that Slo overexpression can lead to downregulation of Wnt signaling.

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