Intracellular scaffolding proteins play important roles in synaptogenesis by linking major components of pre- and postsynaptic machineries with pre- and postsynaptic cell adhesion molecules. Molecules of the extracellular matrix (ECM), secreted from neurons and glial cells, also form scaffolds, although in the extracellular space. These scaffolds are involved in recruitment and stabilization of synaptic components. For instance, ECM molecules may cluster postsynaptic glutamate receptors via direct interactions with the extracellular domains of these receptors in a synapse-specific manner, or accumulate presynaptic Ca2+ channels and growth factors. Furthermore, binding of ECM molecules to cell surface receptors, such as integrins and apolipoprotein E receptor 2, may trigger intracellular signaling cascades resulting in maturation and plasticity of synapses. Additionally, thrombospondins (TSPs) and tenascin-R have prominent effects on formation of synapses via not-yet-identified mechanisms. In this chapter we review available data on synaptogenic activities of ECM molecules, suggesting that these molecules are important for many aspects of synaptic function in the central nervous system (CNS).

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