Dean C, Dresbach T. Neuroligins and neurexins: linking cell adhesion, synapse formation and cognitive function. Trends Neurosci 29: 21-29

Department of Physiology, University of Wisconsin Medical School, Madison, WI 53706, USA.
Trends in Neurosciences (Impact Factor: 13.56). 02/2006; 29(1):21-9. DOI: 10.1016/j.tins.2005.11.003
Source: PubMed


Cell adhesion represents the most direct way of coordinating synaptic connectivity in the brain. Recent evidence highlights the importance of a trans-synaptic interaction between postsynaptic neuroligins and presynaptic neurexins. These transmembrane molecules bind each other extracellularly to promote adhesion between dendrites and axons. This signals the recruitment of presynaptic and postsynaptic molecules to form a functional synapse. Remarkably, neuroligins alone can induce the formation of fully functional presynaptic terminals in contacting axons. Conversely, neurexins alone can induce postsynaptic differentiation and clustering of receptors in dendrites. Therefore, the neuroligin-neurexin interaction has the unique ability to act as a bi-directional trigger of synapse formation. Here, we review several recent studies that offer clues as to how these proteins form synapses and how they might function in the brain to establish and modify neuronal network properties and cognition.

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    • "Even after these initial connections are made, the circuitry is plastic and altered to reflect an animal's experiences. Neurexins encode transmembrane cell adhesion molecules (Ushkaryov et al. 1992) that are vital for the formation, maturation and specification of synapses (Dean and Dresbach 2005). Extensive alternative splicing and variable interactions of neurexins with their respective postsynaptic partners, such as the neuroligins, appear to comprise a code that can direct synapse development towards excitation or inhibition (M Missler and Südhof 1998; Graf et al. 2004; Ben Chih, Engelman, "
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    ABSTRACT: Neurexins are cell adhesion molecules important for synaptic plasticity and homeostasis, though links to sleep have not yet been investigated. We examined effects of neurexin-1 perturbation on sleep in Drosophila, showing that neurexin-1 nulls display fragmented sleep and altered circadian rhythm. Conversely, over-expression of neurexin-1 can increase and consolidate night-time sleep. This is not solely due to developmental effects as it can be induced acutely in adulthood, and is coupled with evidence for synaptic growth. Timing of over-expression can differentially impact sleep patterns, with specific night-time effects. These results show that neurexin-1 is dynamically involved in synaptic plasticity and sleep in Drosophila. Neurexin-1 and a number of its binding partners have been repeatedly associated with mental health disorders, including autism spectrum disorders, schizophrenia and Tourette syndrome, all of which are also linked to altered sleep patterns. How and when plasticity-related proteins such as neurexin-1 function during sleep can provide vital information on the interaction between synaptic homeostasis and sleep, paving the way for more informed treatments of human disorders. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Neuroscience 07/2015; 42(7). DOI:10.1111/ejn.13023 · 3.18 Impact Factor
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    • "Nlgn1 and nlgn2 have been shown to be mainly localized in excitatory glutamatergic and inhibitory GABAergic synapses, respectively, while nlgn3 seems to be present in both and nlgn4 appears to be associated with glycinergic synapses (Budreck and Scheiffele, 2007; Hoon et al., 2011; Varoqueaux et al., 2004). Nlgns and nrxns contain an intracellular PDZ domain that interacts with scaffolding proteins and molecules linked to the intracellular machineries, including the cytoskeleton, vesicle exocytosis and receptor recruitment cascades (Dalva et al., 2007; Dean and Dresbach, 2006; Levinson and El-Husseini, 2005; Missler et al., 2003; Sandi, 2004). In particular, nlgn2 binds to the postsynaptic scaffolding protein gephyrin and to collybistin, which are involved in GABA A -receptor recruitment; thus, nlgn2 may influence GABAergic synaptic properties (Chih et al., 2005; Chubykin et al., 2007; Poulopoulos et al., 2009; Varoqueaux et al., 2006). "
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    ABSTRACT: Early-life stress is a key risk factor for the development of neuropsychiatric disorders later in life. Neuronal cell adhesion molecules have been strongly implicated in the pathophysiology of psychiatric disorders and in modulating social behaviors associated with these diseases. Neuroligin-2 is a synaptic cell adhesion molecule, located at the postsynaptic membrane of inhibitory GABAergic synapses, and is involved in synaptic stabilization and maturation. Alterations in neuroligin-2 expression have previously been associated with changes in social behavior linked to psychiatric disorders, including schizophrenia and autism. In this study, we show that early-life stress, induced by limited nesting and bedding material, leads to impaired social recognition and increased aggression in adult mice, accompanied by increased expression levels of hippocampal neuroligin-2. Viral overexpression of hippocampal neuroligin-2 in adulthood mimics early-life stress-induced alterations in social behavior and social cognition. Moreover, viral knockdown of neuroligin-2 in the adult hippocampus attenuates the early-life stress-induced behavioral changes. Our results highlight the importance of neuroligin-2 in mediating early-life stress effects on social behavior and social cognition and its promising role as a novel therapeutic target for neuropsychiatric disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Psychoneuroendocrinology 02/2015; 55:128-143. DOI:10.1016/j.psyneuen.2015.02.016 · 4.94 Impact Factor
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    • "Cell–cell adhesion plays an integral role in synapse formation and development, synaptogenesis and synaptic plasticity (Bukalo and Dityatev, 2012; Dalva et al., 2007; Li and Sheng, 2003; Washbourne et al., 2004; Yamagata et al., 2003). The most extensively described cell adhesion molecules in synaptic transmission and formation are neurexins, neuroligins, cadherins and members of the immunoglobulin (Ig) superfamily (Craig and Kang, 2007; Dean and Dresbach, 2006; Lisé and El-Husseini, 2006; Scott and Palmer, 1993; Shapiro et al., 2007; Takeichi, 2007). Unlike the classical cell–cell adhesion molecules, the adhesion GPCRs are not characterised by their roles in regulation and/or development of the nervous system. "
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    ABSTRACT: The origin and evolution of the nervous system is one of the most intriguing and enigmatic events in biology. The recent sequencing of complete genomes from early metazoan organisms provides a new platform to study the origins of neuronal gene families. This review explores the early metazoan expansion of the largest integral transmembrane protein family, the G protein-coupled receptors (GPCRs), which serve as molecular targets for a large subset of neurotransmitters and neuropeptides in higher animals. GPCR repertories from four pre-bilaterian metazoan genomes were compared. This includes the cnidarian Nematostella vectensis and the ctenophore Mnemiopsis leidyi, which have primitive nervous systems (nerve nets), the demosponge Amphimedon queenslandica and the placozoan Trichoplax adhaerens, which lack nerve and muscle cells. Comparative genomics demonstrate that the rhodopsin and glutamate receptor families, known to be involved in neurotransmission in higher animals are also widely found in pre-bilaterian metazoans and possess substantial expansions of rhodopsin-family-like GPCRs. Furthermore, the emerging knowledge on the functions of adhesion GPCRs in the vertebrate nervous system provides a platform to examine possible analogous roles of their closest homologues in pre-bilaterians. Intriguingly, the presence of molecular components required for GPCR-mediated neurotransmission in pre-bilaterians reveals that they exist in both primitive nervous systems and nerve-cell-free environments, providing essential comparative models to better understand the origins of the nervous system and neurotransmission. © 2015. Published by The Company of Biologists Ltd.
    Journal of Experimental Biology 02/2015; 218(4):562-571. DOI:10.1242/jeb.110312 · 2.90 Impact Factor
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