Lecture: "How to Build a Synapse: Roles of the Neurexin Complex in Health and Disease"

Fredrik Sterky, Department of Laboratory Medicine, Department of Clinical Chemistry, Wallenberg Centre for Molecular and Translational Medicine, Gothenburg University

How to Build a Synapse: Roles of the Neurexin Complex in Health and Disease

Synapses are the fundamental signal-processing units of the brain, and their assembly and functional specification are orchestrated by adhesion proteins bridging the synaptic cleft. Neurexins are a family of presynaptic adhesion receptors that are well-known to confer genetic risk for brain disorders such as schizophrenia and autism. However, our understanding of their molecular function(s) and regulation remain incomplete. We have employed gene-edited human neurons as a model system to determine how neurexins and their binding partners drive synapse assembly upon the establishment of nascent neuron–neuron contacts. Moreover, proteomic analysis of neurexin complexes in mice revealed a previously unrecognized class of binding partners that may regulate the addition of a functionally critical heparan sulfate modification to neurexins.