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Presentation of the institute



Cell Adhesion Molecules in Synapse Assembly

Team leader: Olivier Thoumine

Olivier Thoumine. After completing an engineering degree in the prestigious Ecole Centrale Paris, I carried out my Ph.D. at Georgia Tech (Atlanta), where I was among the first ones to study integrin-dependent mechanotransduction in the response of endothelial cells to hemodynamic forces. During my post-docs at Institut Curie (Paris) and Ecole Polytechnique Fédérale (Lausanne), I designed new micromanipulation methods to precisely quantify the response of cells to mechanical deformations, which are still used nowadays. After my recruitment by the CNRS in 2001 in the team of D. Choquet (Bordeaux), I developed biomimetic systems coupled with high resolution imaging and predictive biophysical models, to probe the role of the cytoskeleton and adhesion proteins in growth cone motility and synaptogenesis.

Contacts: Olivier Thoumine, tel. +33 (0)5 33 51 47 04

Project Summary

My team first demonstrated a fundamental role of the mechanical coupling between N-cadherin adhesion and the flowing actin cytoskeleton in growth cone migration and dendritic spine morphogenesis (Bard et al., J Neurosci 2008; Giannone et al., Trend Cell Biol 2009; Chazeau et al., Mol Biol Cell 2015; Garcia et al., PNAS 2015). Second, we deciphered a multi-step model of synapse assembly mediated by the neurexin-neuroligin adhesion complex, by which a strong NRX1/NLG1 binding (Saint-Michel et al., Biophys J 2009) induces the preferential recruitment of the scaffolding molecule PSD-95 versus gephyrin through tyrosine phosphorylation of NLG1 (Giannone et al., Cell Reports 2013). These scaffolds then act as platforms for the recruitment of surface-diffusing AMPA receptors (Heine et al., PNAS 2008; Mondin et al., J Neurosci 2011; Letellier et al, in preparation). In parallel, we set up an original system of neuronal cultures on micro-patterned substrates coated with adhesion proteins for the screening of synapse differentiation (Czöndör et al., Nat Comm 2013), and patented this method in collaboration with the company CYTOO (Grenoble). We also identified novel microRNAs regulators of AMPA receptor translation in conditions of homeostatic synaptic scaling (Letellier et al, Nat Neurosci 2014), which might be used in the future as novel therapeutic agents to control the excitation/inhibition balance in the brain.

On the methodological side, we developed a novel labeling technique based on 3-nm fluorescently-conjugated monomeric streptavidin to track recombinant enzymatically-biotinylated membrane molecules, compatible with a wide range of super-resolution imaging techniques. We applied this technique to map the dynamic organization of NRX/NLG trans-synaptic contacts at the nanoscale (Chamma et al., Nat Comm, in press). To better interpret our single molecule tracking data, we generated Monte Carlo computer simulations allowing a unified description of the trafficking of AMPA receptors at synapses (Czöndör et al., PNAS 2012).