CONNECTING VOLTAGE-GATED POTASSIUM CHANNELS TO TRANSCRIPTIONAL AND TRANSLATIONAL REGULATION

Potassium (K+) channels are found in the majority of cells in almost every organism, where they regulate a wide variety of physiological functions in response to environmental stimuli. The goal of TRANSION is to confirm our hypothesis that physical coupling between voltage-gated potassium (K+) channels in the Shaker-type (Kv1) family and specific transcription factors (TFs) provides a widespread signaling checkpoint that coordinates information from different stimuli and orchestrates appropriate transcriptional and translational responses. This ground-breaking program will reveal novel roles for ion channels in regulating signal transduction, changing the paradigm by which cells adjust transcriptional programs and protein translation in response to environmental change. The premise that TFs are directly regulated by their association with voltage-gated ion channels is unprecedented, and its verification will disclose unique roles for this important class of evolutionarily conserved K+ channels as well as these families of TFs that control physiologically and pathologically relevant processes. Gaining insight into the underlying mechanism may also lead to the development of innovative therapies against a number of pathologies, given that ion channels can be modulated by both inhibitors and activators at picomolar concentrations. By developing tools to probe the relevance of this novel signaling pathway, TRANSION will uncover mechanisms, identify players, and reveal structural information that will further our understanding of transcription and translation in vivo. It will also establish connections between different fields of research and provide a springboard to ask new questions. TRANSION will deliver a unifying conceptual framework to understand how ion channels can regulate protein translation.