A current view on contactin-4, -5, and -6: Implications in neurodevelopmental disorders.

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record.Contactins (Cntns) are a six-member subgroup of the immunoglobulin cell adhesion molecule superfamily (IgCAMs) with pronounced brain expression and function. Recent genetic studies of neuropsychiatric disorders have pinpointed contactin-4 (CNTN4), contactin-5 (CNTN5) and contactin-6 (CNTN6) as candidate genes in neurodevelopmental disorders, particularly in autism spectrum disorders (ASDs), but also in intellectual disability, schizophrenia (SCZ), attention-deficit hyperactivity disorder (ADHD), bipolar disorder (BD), alcohol use disorder (AUD) and anorexia nervosa (AN). This suggests that they have important functions during neurodevelopment. This suggestion is supported by data showing that neurite outgrowth, cell survival and neural circuit formation can be affected by disruption of these genes. Here, we review the current genetic data about their involvement in neuropsychiatric disorders and explore studies on how null mutations affect mouse behavior. Finally, we highlight to role of protein-protein interactions in the potential mechanism of action of Cntn4, -5 and -6 and emphasize that complexes with other membrane proteins may play a role in neuronal developmental functions.Authors of this review were supported by EU-AIMS (European Autism Interventions), which receives support from the Innovative Medicines Initiative Joint Undertaking under Grant agreement no.115300, there sources of which are composed of financial contributions from the European Union's Seventh Framework Programed Grant (P7/2007–2013), from the European Federation of Pharmaceutical Industries and Associations Companies' in-kind contributions, and from Autism Speaks. (K.T.E.K. and J.P.H.B.), by a Fellowship from JSPS (A.O.A. and A.Z)