LGI1-mediated modulation of neuronal excitability – LoGIK

Our proposal addresses the question of how LGI1, an extracellular protein secreted by neurons and involved in neurological diseases such as epilepsies or limbic encephalitis, controls intrinsic neuronal excitability and synaptic transmission through the regulation of Kv1 channel expression in the axon. We propose to i) examine the molecular interplay between LGI1 and Kv1 channels, ii) investigate whether perturbed membrane expression of Kv1 is a common pathogenic mechanism shared between genetic and autoimmune diseases involving LGI1, iii) determine the role of LGI1 in activity-dependent plasticity in intrinsic excitability involving Kv1 channels and iv) decipher the structural details of LGI1 in molecular complexes. Our project will not only help provide new knowledge about the regulatory mechanisms of axonal Kv1 channels but it will also help define new therapeutic strategies for epilepsy.