Cell adhesion molecules: signalling functions at the synapse

Abstract

Many cell adhesion molecules are localized at synaptic sites in neuronal axons and dendrites. These molecules bridge pre-and postsynaptic specializations but do far more than simply provide a mechanical link between cells. In this review, we will discuss the roles these proteins have during development and at mature synapses. Synaptic adhesion proteins participate in the formation, maturation, function and plasticity of synaptic connections. Together with conventional synaptic transmission mechanisms, these molecules are an important element in the trans-cellular communication mediated by synapses.CNS synapses are specialized sites of cell-cell contact that mediate the transmission of information between neurons. Synapses are a key site of regulation within neural networks and are characterized by multi-protein complexes arranged at tightly apposed pre-and postsynaptic terminals. Communication between neurons at synapses is mediated primarily by neurotransmitter release and by the gating of postsynaptic receptor ion channels, but a growing body of evidence indicates that signalling is also mediated by adhesion molecules that interact in a homo-or heterophilic fashion across the synaptic cleft. As at other cell-cell junctions, such as epithelial tight junctions or the immune synapse, research in a variety of neuronal subtypes has shown that synaptically localized cell adhesion molecules (SAMs) are not merely static structural components but are often dynamic regulators of synapse function. When pairs of SAMs interact, they can induce the formation of new synapses or modulate the function of existing synapses through signalling cascades or secondary protein-protein interactions. Numerous studies indicate that interactions between specific SAMs can control synapse formation, regulate dendritic spine morphology, modify synaptic receptor function and modulate synaptic plasticity. So, SAMs can mediate physical interactions between cells and act at multiple steps in the life of a synapse (FIG. 1).Here, we focus on well-studied classes of SAMs that have roles at both developing and mature synapses, namely neurexins and neuroligins, EphBs and ephrin-Bs, immunoglobulinCorrespondence to: M.B.D. dalva@mail.med.upenn.edu. Competing interests statementThe authors declare no competing financial interests. Note added in proofIn a recently published manuscript, Futai et al. 144 demonstrate that trans-synaptic β-neurexin-neuroligin interactions can modulate presynaptic function. The authors show that overexpression or knockdown of PSD-95 in the postsynaptic cell modulates presynaptic release probability, and that these effects are blocked when trans-synaptic β-neurexin-neuroligin signalling is disrupted. This paper provides further evidence that SAMs act to regulate synaptic function. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript (Ig)-containing cell adhesion molecules and cadherins. We discuss the ways in which these proteins seem to control discrete aspects of synaptic develop...

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