Abstract
IntroductionNeuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing.MethodsIn this study, we analyzed the functional effect of these missense variations by in vitro experiment via the stable HEK293 cells expressing wild‐type and mutant neuroligin.ResultsWe found that the four mutations did not significantly impair the expression of neuroligin 3 and neuroligin 4X, and also did not measurably inhibit the neurexin 1–neuroligin interaction. These variants might play a modest role in the pathogenesis of autism or might simply be unreported infrequent polymorphisms.ConclusionOur data suggest that these four previously described neuroligin mutations are not primary risk factors for autism.
Highlights
Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses
Neuroligins are postsynaptic cell adhesion molecules that are involved in the NRXN-NLGN-SHANK pathway, most likely associated with synaptogenesis and the balance between synapse excitation and inhibition (Bang & Owczarek, 2013; Mackowiak, Mordalska, & Wedzony, 2014)
Several other mutations in the NLGN3, NLGN4X, and NLGN4Y genes have been reported to be related to autism (Chih, Afridi, Clark, & Scheiffele, 2004; Daoud et al, 2009; Kuroda et al, 2014; Laumonnier et al, 2004; Lawson-Yuen et al, 2008; Talebizadeh et al, 2006; Yan et al, 2005, 2008)
Summary
Neuroligins are postsynaptic cell adhesion molecules that are involved in the NRXN-NLGN-SHANK pathway, most likely associated with synaptogenesis and the balance between synapse excitation and inhibition (Bang & Owczarek, 2013; Mackowiak, Mordalska, & Wedzony, 2014). Several other mutations in the NLGN3, NLGN4X, and NLGN4Y genes have been reported to be related to autism (Chih, Afridi, Clark, & Scheiffele, 2004; Daoud et al, 2009; Kuroda et al, 2014; Laumonnier et al, 2004; Lawson-Yuen et al, 2008; Talebizadeh et al, 2006; Yan et al, 2005, 2008). The four variants might impair the functional properties of neuroligin related to synaptic homeostasis, thereby increasing predisposition to autism. To test this hypothesis, here we analyzed the functional effect of these four missense variants
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