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Séminaire impromptu - Jonathan ElegheertMind the Gap: Structure, Function and Engineering of Synaptic Organizer Protein Complexes (IINS team leader candidate)

Abstract :

 The human brain consists of billions of neuronal cells that assemble into networks to support cognitive functions.
Synapses are specialized cellular junctions that form the dedicated sites of communication between these neurons.
Synaptic organizer protein complexes span the synaptic cleft to link pre- and postsynaptic membranes, and to induce synaptic differentiation and modulate neuronal signaling.

In this talk, I will focus on the structural biology of protein complexes within the extended network of the neuroligin–neurexin (NL–NRX) signaling hub. NL–NRX complexes specify formation and function of excitatory and inhibitory synapses throughout the brain and aberrant signaling in this pathway is strongly linked to disorders such as autism and schizophrenia.
I will then illustrate how protein structure can be used to inform the design of synthetic synaptic organizer molecules that may present a novel therapeutic avenue for neurodegenerative diseases that are characterized by loss of synapses.
Throughout the talk, I will emphasize the synergy of structural biology with techniques from molecular, cellular and behavioral neuroscience.

Selected publications

Structural mechanism for modulation of synaptic neuroligin-neurexin signaling by MDGA proteins. Elegheert J(*), Cvetkovska V, Clayton A, Heroven C, Vennekens KM, Smukowski SN, Re- Publications gan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR. Neuron. 2017 Aug 16;95(4):896-913.

Structural basis for integration of GluD receptors within synaptic organizer complexes. Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR. Science. 2016 Jul 15;353(6296):295-9.