title: Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders.
abstract: Synaptic cell adhesion molecules (SCAMs) are a functional category of cell adhesion molecules that connect pre- and postsynapses by the protein-protein interaction via their extracellular cell adhesion domains. Countless numbers of common genetic variants and rare mutations in SCAMs have been identified in the patients with autism spectrum disorders (ASDs). Among these, NRXN and NLGN family proteins cooperatively function at synaptic terminals both of which genes are strongly implicated as risk genes for ASDs. Knock-in mice carrying a single rare point mutation of NLGN3 (NLGN3 R451C) discovered in the patients with ASDs display a deficit in social interaction and an enhancement of spatial learning and memory ability reminiscent of the clinical phenotype of ASDs. NLGN4 knockout (KO) and NRXN2α KO mice also show a deficit in sociability as well as some specific neuropsychiatric behaviors. In this review, we selected NRXNs/NLGNs, CNTNAP2/CNTNAP4, CNTN4, ITGB3, and KIRREL3 as strong ASD risk genes based on SFARI score and summarize the protein structures, functions at synapses, representative discoveries in human genetic studies, and phenotypes of the mutant model mice in light of the pathophysiology of ASDs.
authors.affiliation: Department of Biological Sciences, Forman Christian College, Zahoor Elahi Rd, Lahore, 54600, Pakistan.
authors.forename: Deeba Noreen
authors.initials: DN
authors.lastname: Baig
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yanagawa
authors.affiliation: Department of Molecular and Cellular Physiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan; Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Matsumoto, 390-8621, Japan; PRESTO, JST, Saitama, 332-0012, Japan. Electronic address: ktabuchi@shinshu-u.ac.jp.
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Tabuchi
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000235:genetics* / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics* / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans
chemical_list: D015816:Cell Adhesion Molecules, Neuronal
keywords: Autism spectrum disorders; Mouse models; Neurexin; Neuroligin; Synaptic cell adhesion molecules