Neurexins and neuroligins: A synaptic code for neuronal wiring that is implicated in autism

Abstract

Neurexins and neuroligins are neuronal cell adhesion molecules (CAMs), which are specifically expressed in the nervous system and particularly in the brain. Presynaptic neurexins interact with postsynaptic neuroligins in a Ca2+-dependent manner and form trans-synaptic adhesion complexes, which are implicated in synaptogenesis. Differential splicing of neurexin and neuroligin transcripts results in a large variety of isoforms. These isoforms differ in their binding affinities and ligand specificities and are differentially distributed in the central nervous system. This may reflect a synaptic code, which along with other neuronal adhesion molecules determines the wiring diagram of neuronal connections in the brain. Mouse genetic studies suggest that neurexins and neuroligins are involved in the stabilization of transient, rather than the formation of de novo synapses. Mutations in neurexin and neuroligin genes, as well as their downstream signaling molecules, have been identified in patients with mental retardation and autism spectrum disorders. Mice with corresponding mouse mutations represent new promising experimental models, which display the typical phenotypes associated with these diseases. The first results obtained from these models suggest that a disruption of the balance between excitatory and inhibitory neurotransmission (E/I) is one of the potential pathophysiological mechanisms for autism and mental retardation.