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Synaptic functions of glycans

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  • Synaptic functions of glycans

    January 07, 2014 16:00 - 17:00 Alexey Semyanov & Thomas McHugh

    The tremendous structural diversity of glycan chains allows for immense combinatorial possibilities that might underlie the fine-tuning of cell-cell and cell-matrix interactions. Indeed, the roles of several glycans in formation and function of synapses have been highlighted. The polysialylated form of NCAM in association with heparan sulfate proteoglycans regulates formation of synapses in an NMDA and FGF receptor-dependent manner (Dityatev et al., 2004). Polysialic acid (PSA) is a necessary and sufficient part of NCAM for normal induction of long-term potentiation in the CA1 region of the hippocampus (reviewed by Hildebrandt and Dityatev, 2013). PSA potentiates AMPA receptor-mediated currents in immature neurons and astrocytes and inhibits GluN2B-containing NMDA receptors. On the other hand, the effects of the extracellular matrix glycoprotein tenascin-R on GABAergic perisomatic inhibition are mediated by the associated HNK-1 carbohydrate, whose binding to GABAB receptors may regulate K+ homeostasis in perisomatic inhibitory synapses (reviewed by Dityatev et al., 2010). HNK-1 and chondroitin sulfates are enriched in the extracellular matrix of perineuronal nets surrounding fast-spiking perisomatic inhibitory interneurons. Recordings from these interneurons after enzymatic removal of chondroitin sulfates revealed that these beautiful structures regulate excitability of interneurons (reviewed by Dityatev et al., 2010). More recent data indicate that another glycan, hyaluronic acid, regulates synaptic plasticity by modulation of L-type voltage gated Ca2+ channels (Kochlamazashvili at al., 2010). These studies suggest that glycans may mediate interplay between the ECM/cell adhesion molecules and ion channels, and affect multiple aspects of neuronal development and activity.
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