Conférence scientifique | Centre de recherche du CHU Sainte-Justine
Conférence de Margaret Elizabeth Ross, MD, PhD, directrice du Centre de neurogénétique, Institut de recherche sur le cerveau et l'esprit, Weill Cornell Medicine, New York, NY
Happloinsufficiency of LIS1 causes a severe human brain malformation called lissencephaly. Though structurally similar to Gbeta proteins, the most intensively studied LIS1 function is its relationship with microtubules and its interaction with the minus end directed dynein protein motor and with dynein complex proteins including NUDEL, p150Glued dynactin subunit, and CLIP170. In this presentation we will discuss the impact of LIS1 on Rho family GTPase activity and the actin based cytoskeleton as it relates not only to neuronal migration but also LIS1 roles once migration is over. These include NMDA receptor signal transduction, synaptogenesis, neurite spine turnover and maintenance of neuronal connectivity and survival. These effects have profound impact on behavior. A picture for LIS1 is emerging as a hub protein that promotes optimal synaptic plasticity and excitatory-inhibitory balance with relevance for neuropsychiatric disorders including autism spectrum, schizophrenia and dementia.