Figure 1.

Proposed model of interactions between ion channels and Wnt signaling. (A) KCNQ1 (or hERG) and ClC-2 are associated to E-cadherin and β-catenin at adherent junctions (AJ). Activity of these two channels maintain membrane potential hyperpolarized, which could be a favorable condition for AJ stability, and sequestration of β-catenin at the plasma membrane. CFTR activity maintains intracellular pH, preventing from pHi alkalinisation which induces Dishevelled-dependant inhibition of Destruction Complex (DC). These four channels participate in maintaining Wnt signaling in OFF-state, in which β-catenin is either degraded or sequestrated and cannot translocate into the nucleus to induce Wnt target genes. (B) Ca²⁺ entry through TRPC5, TRPM4, TRPV4 and P2X7 channels, induces AKT activation. Thus, AKT phosphorylates GSK3-β which becomes inhibited and subsequently allows the cytosolic accumulation of β-catenin. ASIC1a, by maintaining an acidic pH, decreases β-catenin phosphorylation and ubiquitination, preventing its degradation and inducing a cytosolic accumulation.