Traduction: G.M.
Brain Res Bull. 2016 Oct 12. pii: S0361-9230(16)30344-6. doi: 10.1016/j.brainresbull.2016.10.006. [Epub ahead of print]
Distortion of the normal function of synaptic cell adhesion molecules by genetic variants as a risk for autism spectrum disorders
Baig DN1, Yanagawa T2, Tabuchi K3.
Author information
- 1Department of Biological Sciences, Forman Christian College, Zahoor Elahi Rd, Lahore, 54600, Pakistan.
- 2Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Tsukuba, Ibaraki, 305-8575, Japan.
- 3Department 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
Abstract
Les
molécules synaptiques d'adhésion cellulaire (les SCAMS) sont une
catégorie fonctionnelle de molécules d'adhésion cellulaire qui se
connectent avant et après les synapses par l'interaction protéine-protéine par
l'intermédiaire de leurs domaines extracellulaires d'adhésion
cellulaire. Un
nombre incalculable de variantes génétiques communes et de mutations rares
dans SCAM ont été identifiés chez les "patients" avec troubles du
spectre de l'autisme (TSA). Parmi
ceux-ci, les protéines de la famille NRXN et NLGN fonctionnent en
coopération dans les terminaux synaptiques, deux des gènes qui sont
fortement impliqués comme des gènes à risque de TSA. Des souris Knock-in porteuses d'une mutation ponctuelle unique rare de NLGN3
(NLGN3 R451C) découvert chez les "patient"s avec de TSA montrent un
déficit dans l'interaction sociale et une amélioration de
l'apprentissage spatial et la capacité de mémoire qui rappelle le
phénotype clinique des TSA. Des souris NLGN4
KO (KO) et des souris KO NRXN2α montrent également un déficit de
sociabilité ainsi que certains comportements neuropsychiatriques
spécifiques. Dans
cette revue, nous avons sélectionné NRXNs / NLGNs, CNTNAP2 / CNTNAP4,
CNTN4, ITGB3 et KIRREL3 comme gènes de base à haut risque de TSA sur le
score SFARI et résumons les structures des protéines, des fonctions au
niveau des synapses, des découvertes représentatives dans les études
génétiques humaines, et les phénotype des souris modèles mutantes à la lumière de la physiopathologie des TSA.
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 base 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.
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 base 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.
Copyright © 2016. Published by Elsevier Inc.
- PMID: 27743928
- DOI: 10.1016/j.brainresbull.2016.10.006
