title: A current view on contactin-4, -5, and -6: Implications in neurodevelopmental disorders.
abstract: 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.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands; University of Exeter Medical School, Wellcome Wolfson Centre for Medical Research, RILD Building, Barrack Road, Exeter EX2 5DW, UK.
authors.forename: Asami
authors.initials: A
authors.lastname: Oguro-Ando
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands; RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Amila
authors.initials: A
authors.lastname: Zuko
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands.
authors.forename: Kristel T E
authors.initials: KTE
authors.lastname: Kleijer
authors.affiliation: Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Universiteitsweg 100, 3584CG Utrecht, The Netherlands. Electronic address: j.p.h.burbach@umcutrecht.nl.
authors.forename: J Peter H
authors.initials: JPH
authors.lastname: Burbach
mesh_terms: D000818:Animals; D058966:Contactins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000073658:Loss of Function Mutation; D065886:Neurodevelopmental Disorders / Q000235:genetics / Q000378:metabolism*
chemical_list: D058966:Contactins
keywords: ADHD; Alcohol use disorder; Anorexia nervosa; Autism; Bipolar disorder; Cell adhesion molecules; Contactin; IgCAMs; Neurodevelopmental disorder; Neuropsychiatric disorder; Schizophrenia