Cell Adhesion Molecules in Synapse Assembly
Team Leader : Olivier Thoumine
After completing an engineering degree at Ecole Centrale Paris, I carried out my Ph.D. at Georgia Tech (Atlanta), where I studied 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 micromanipulation methods to quantify the response of cells to mechanical deformations. After my recruitment by the CNRS 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. I created an independent team in 2010, focusing on the dynamics and function of synaptic adhesion molecules. The team now oscillates between 10-12 people including permanent researchers, technicians, post-docs, PhD and Master students.
Contact: Olivier Thoumine, tel. +33 (0)5 33 51 47 04; e-mail: Olivier.firstname.lastname@example.org
Elucidation of the complex map of neural connectivity in the mammalian brain is one of the major goals of neuroscience research. Fundamental to such efforts, and to the comprehension of neurological disorders, is to gain an understanding of the mechanisms that form and maintain synaptic connections. Adhesion proteins play important roles in these processes, not only by establishing a structural linkage between pre- and post-synaptic membranes, but also by instructing the differentiation of synaptic compartments through the connection to specific molecular partners, regulated by signaling mechanisms.
In this context, our team aims at better understanding the role of adhesion molecules in synapse assembly and differentiation, with a focus on specific proteins including N-cadherin, neurexins, neuroligins, LRRTMs, and their associated partners (MDGAs, actin cytoskeleton, scaffolding proteins, glutamate receptors). We are particularly interested in characterizing the membrane dynamics, binding kinetics, nanoscale organization, and signaling mechanisms associated with these molecular complexes. Our working models, both isolated from rodent brains, are dissociated hippocampal neurons which bear good optical properties for super-resolution imaging, and organotypic hippocampal slices that have well-preserved dendritic architecture and synaptic connectivity.
In silico and in vitro methods to quantify interaction dynamics between synaptic proteinsMORE
Regulation of neuroligin-1 dynamics, organization, and function at the synapseMORE
Interplay between cell adhesion molecules and neuronal activity in synaptic circuit dynamicsMORE
Epigenetic and transcriptomic regulation of synaptic adhesion molecules during development and plasticityMORE
Controlling synapse differentiation with light - eLife, April 2020
Optogenetic control of excitatory post-synaptic differentiation through neuroligin-1 tyrosine phosphorylation.
Neuroligins (Nlgns) are adhesion proteins mediating trans-synaptic contacts in neurons. However, conflicting results around their role in synaptic differentiation arise from the various techniques used to manipulate Nlgn expression level. Orthogonally to these approaches, we triggered here the phosphorylation of endogenous Nlgn1 in CA1 mouse hippocampal neurons using a photoactivatable tyrosine kinase receptor (optoFGFR1). Light stimulation for 24 hr selectively increased dendritic spine density and AMPA-receptor-mediated EPSCs in wild-type neurons, but not in Nlgn1 knock-out neurons or when endogenous Nlgn1 was replaced by a non-phosphorylatable mutant (Y782F). Moreover, light stimulation of optoFGFR1 partially occluded LTP in a Nlgn1-dependent manner. Combined with computer simulations, our data support a model by which Nlgn1 tyrosine phosphorylation promotes the assembly of an excitatory post-synaptic scaffold that captures surface AMPA receptors. This optogenetic strategy highlights the impact of Nlgn1 intracellular signaling in synaptic differentiation and potentiation, while enabling an acute control of these mechanisms.
Authors: Letellier M, Lagardère M, Tessier B, Janovjak H, Thoumine O.
FluoSim, Matthieu Lagardère and Olivier Thoumine in Scientific Reports - November 2020
We introduce fast, robust, and user-friendly software called FluoSim that allows for real time simulation of membrane protein dynamics in live-cell imaging and super-resolution modalities. We also show that FluoSim can be used to produce large virtual data sets for training deep neural networks for image reconstruction. This software should thus be of great interest to a wide community specialized in imaging methods applied to cell biology and neuroscience, with the common aim to better understand membrane dynamics and organization in cells. FluoSim is freely available on the website of the publisher Scientific Reports.
FluoSim: simulator of single molecule dynamics for fluorescence live-cell and super-resolution imaging of membrane proteins
- Authors: Lagardère M, Chamma I, Bouilhol E, Nikolski M, Thoumine
- Scientific Reports 10, 19954 (2020). https://doi.org/10.1038/s41598-020-75814-y
+ See the movie here
Simulation of a Fluorescence Recovery After Photobleaching (FRAP) experiment.
The movie generated with FluoSim shows the distribution of surface receptors in a dendritic segment, with specific accumulation in post-synaptic areas (red color).
Receptors are photobleached at t = 5 sec in two specific synapses. Note the fluorescence recovery over time (total 60 sec), due to receptor diffusion and turnover.
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|CHAUVINEAU Benjamin||Technical email@example.com||+33533514700|
|DESQUINES Chloé||Technical firstname.lastname@example.org||+33533514700|
|ROUGLAN Vanessa||Technical email@example.com||+33533514700|
|TESSIER Beatrice||Technical firstname.lastname@example.org||+33533514729|
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|GASSAMA Yadaly||PhD email@example.com||+33533514700|
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