Crystal-clear view of a key neuronal receptor opens door for new, targeted drugs

During brain development, billions of neuron nerve cells must find their accurate pathway in the brain in order to form trillions of neuronal circuits enabling cognitive, sensory and emotional wellbeing. To achieve this remarkable precision, migrating neurons use special protein receptors that sense the environment around them and guide the way so these neurons and their long extensions stay on the right path and avoid faulty turns. Rare defects in these neuronal guidance proteins can result in severe neurological conditions such as ataxia and epilepsy. In a new study published in Cell, Bar-Ilan University researchers and collaborators report on their discovery of the intricate molecular mechanism that allows the guidance receptor Robo to react to signals in its environment while avoiding premature activity that can lead to harmful outcomes. One of the most important protein signaling systems that control neuronal guidance consists of the cell surface receptor Robo and its cognate external guidance cue Slit. The deficit of either of these proteins results in defects in brain structure and function. For example, their absence compromises the brain's ability to form the correct connection across the corpus callosum, which is the region where neuronal extensions from the two brain hemispheres cross paths to innervate opposite sides of the body, a fundamental attribute of bilateral creatures.