Contact: Françoise COUSSEN
Tel. (+33)5 05 33 51 47 34
The AMPAR Trafficking axis is integrated into the Dynamics of Synapse Organization and Function group .
This activity is headed by Françoise Coussen (DR2, senior researcher) and currently involves Emilie Hangen (Post-doctoral fellow) and Azra Zamri (PhD student). AMPARs are organized as macromolecular complexes comprised of the pore forming subunits (GluA) surrounded with a set of transmembraneous auxiliary subunits such as TARPs, Cornichon, CKAMP44 and recently characterized Shisa6 by our group. The contribution of each independent auxiliary on the trafficking, localization in and out the synapse and physiology of AMPARs is still poorly understood. Our goal is to study how auxiliary proteins interact in order to ensure the correct life of the ionotropic subunits, from intracellular transport to stabilization at the postsynaptic density. Our different topics studied are:
We use classical technics such as biochemistry, molecular biology, cell biology, cell neuro-biology coupled with high resolution microscopy and video-microscopy. We have set up a new imaging technics in order to visualize directed movements of small objects. The imaging data is complemented by semi-automated analysis performed with in house routines programmed with ImageJ.
This activity is currently funded by the ANR Blanche "PAINT " 2015-2019: F. Coussen (Coord). AMPA receptor transport and the ERC (2014-2018) grant ADOS (Ampa receptor Dynamic Organization and Synaptic transmission in health and disease).
Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity.
Klaassen RV, Stroeder J, Coussen F, Hafner AS, Petersen JD, Renancio C, Schmitz LJ, Normand E, Lodder JC, Rotaru DC, Rao-Ruiz P, Spijker S, Mansvelder HD, Choquet D, Smit AB. Nat Commun. 2016 Mar (Klaassen RV, Stroeder J, Coussen F, co first-authors; Choquet D, Smit AB, co last-authors)
Lengthening of the Stargazin Cytoplasmic Tail Increases Synaptic Transmission by Promoting Interaction to Deeper Domains of PSD-95..
Hafner AS, Penn AC, Grillo-Bosch D, Retailleau N, Poujol C, Philippat A, Coussen F, Sainlos M, Opazo P, Choquet D. Neuron. 2015 Apr
Glutamate-induced AMPA receptor desensitization increases their mobility and modulates short-term plasticity through unbinding from Stargazin.
Constals A, Penn AC, Compans B, Toulmé E, Phillipat A, Marais S, Retailleau N, Hafner AS,Coussen F, Hosy E, Choquet D. Neuron. 2015 Feb
CaMKII-dependent phosphorylation of GluK5 mediates plasticity of kainate receptors.
Carta M, Opazo P, Veran J, Athané A, Choquet D, Coussen F, Mulle C. EMBO J. 2013 Feb
Regulation of AMPA receptor surface trafficking and synaptic plasticity by a cognitive enhancer and antidepressant molecule.
Zhang, H., Etherington, L., Hafner, A.S., Belelli, D., Coussen, F., Delagrange, P., Chaouloff, F., Spedding, M., Lambert, J., Choquet, D. and Groc, L. (2012). Molecular Psychiatry, June 26, 1-14.
Deborah Huyghe (PhD student and post-doctoral fellow) - Cédric Renancio (PhD student) - Amandine Philippat (assistant engineer)