18 Novembre 2019 - 11H

Jonathan ELEGHEERT, Interdisciplinary Institute for NeuroScience (IINS), Bordeaux 

Lieu : Salle B501

Résumé : Synapses are the specialized cellular junctions that form the basic units of communication between neuronal cells.

Synaptic organizer proteins, which include specialized cell adhesion molecules (CAMs) and secreted extracellular scaffolding proteins (ESPs), contribute to the specification of synapse identity and function by forming molecular bridges that span the synaptic cleft and mediate bi- directional signaling.

I will present structural and functional studies focusing on interactions of the pre-synaptic neurexin (Nrx) signaling hub. Soluble secreted cerebellin (Cbln) proteins physically connect presynaptic Nrx to postsynaptic ?-subtype (GluD) ionotropic glutamate receptors (iGluRs). This synapse-spanning complex promotes synapse formation and activates downstream GluD2 signaling, leading to induction of synaptic plasticity at cerebellar synapses. The Nrx–Cbln–GluD complex illustrates how protein and small-molecule ligands synergistically control iGluR function, a concept that is likely to be more generally applicable.

Additionally, I will present new data showing that synthetic synaptic organizer proteins with defined binding specificities can be applied in models of neuronal disease that are characterized by dysfunction and loss of synapses. One such molecule, CPTX, directly links presynaptic Nrx and postsynaptic AMPA-subtype iGluRs and restores excitatory synaptic functions in model mice for cerebellar ataxia, Alzheimer’s disease and spinal cord injury, demonstrating the possibility to develop synthetic synaptic organizer proteins to repair neural circuits.

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Séminaire organisé par l'unité Neuroscience Paris-Seine