In C. elegans, 47 genes code for K2P channel subunits. We focus on channels expressed in the neuromuscular system because their deregulation has profound behavior effects. By using forward genetic screens, we have identified conserved genes that regulate K2P channel function in various ways. We have analyzed the distribution of K2Ps in these mutants by using state-of-the-art genome engineering to label channels with fluorescent proteins (e.g. mScarlet). Strikingly, we have found that three K2P channels, which are expressed in the same muscle cell, have distinct subcellular distributions, and that specific genetic programs control the localization of each channel. In addition, by using electrophysiological techniques, we have identified an unconventional K2P channel that is selective for sodium instead of potassium, while retaining all the structural features of traditional K2P channels. Finally, we will show preliminary data demonstrating that K2P channels can be activated by mutating a single conserved amino-acid, and that these mutations can be integrated into the genome by CRISPR/Cas9 genome engineering, resulting in striking phenotypes.

Contact :ibs.seminaires@ibs.fr