The role of neurexins and neuroligins in autism

Autistic spectrum disorder (ASD) is a common, chronic psychiatric disorder for which the current generation of therapeutics are limited in their success at alleviating the neurobehaviors. While it is well established that both genetic and environmental factors contribute to the disorder, there is a lack of understanding about how ASD alters multiple domains of brain function. Identifying genes that are associated with ASD, and then relating how these genetic alterations affect brain structure and function is important to furthering our ability to design treatment and prevention strategies. Recent genome screening using copy number variant (CNV) analysis has identified deletions and duplications within the neurexin and neuroligin genes in patients with ASDs, highlighting their potential importance in ASD research. Neurexins and neuroligins are synaptic cell adhesion molecules and are found at the presynapse and postsynapse, respectively, of both excitatory and inhibitory cells. Neuroligins and leucine-rich repeat transmembranes bind to neurexins and convey a role in synaptic function and maintenance. However, little is known about how alterations within the genes encoding these proteins disrupt biological processes. Here we discuss the functional role of neurexins and neuroligins, the genetic evidence for their involvement in ASD and studies with transgenic mice to elucidate the consequences of these mutations.