GABAB receptor phosphorylation regulates KCTD12-induced K⁺ current desensitization.
Bottom Line: Receptor-activated K(+) currents desensitize in the sustained presence of agonist to avoid excessive effects on neuronal activity.GABAB receptor activity reduces protein kinase-A activity, which reduces phosphorylation of serine-892 in GABAB2 and promotes receptor degradation.This cross-regulation of serine-892 phosphorylation and KCTD12 activity sharpens the response during repeated receptor activation.
Affiliation: Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.Show MeSH
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Mentions: Since KCTD12 binds to GB2 in proximity of the PKA phosphorylation-site S892 (Fig. 1A), phosphorylation of S892 may influence the ternary receptor/KCTD12/G-protein complex and vice versa, KCTD12 may influence S892 phosphorylation. We therefore addressed whether PKA regulates KCTD12-induced K+ current desensitization. We found that PKA phosphorylation of S892 reduces KCTD12-induced K+ current desensitization in heterologous cells and cultured hippocampal neurons. Mechanistically, S892 phosphorylation induces a conformational change in the GABAB receptor/KCTD12 complex that slows KCTD12-induced desensitization. Reciprocally, the binding of KCTD12 promotes phosphorylation of S892, consistent with previous data showing that KCTD12 stabilizes receptors at the cell surface .
Affiliation: Department of Biomedicine, University of Basel, 4056 Basel, Switzerland.