A molecular switch controls the impact of cholesterol on a Kir channel.
Valentina CorradiAnna N BukiyaWilliams E MirandaMeng CuiLeigh D PlantDiomedes E LogothetisD Peter TielemanSergei Yu NoskovAvia Rosenhouse-DantskerPublished in: Proceedings of the National Academy of Sciences of the United States of America (2022)
SignificanceCholesterol is one of the main components found in plasma membranes and is involved in lipid-dependent signaling enabled by integral membrane proteins such as inwardly rectifying potassium (Kir) channels. Similar to other ion channels, most of the Kir channels are down-regulated by cholesterol. One of the very few notable exceptions is Kir3.4, which is up-regulated by this important lipid. Here, we discovered and characterized a molecular switch that controls the impact (up-regulation vs. down-regulation) of cholesterol on Kir3.4. Our results provide a detailed molecular mechanism of tunable cholesterol regulation of a potassium channel.