Team : CHOQUET
Research Projects
Impact of auxiliary proteins on AMPAR transport, trafficking and physiology (Françoise Coussen).
Project Leader(s): Françoise Coussen
Contact: Françoise COUSSEN
Tel. (+33) 5 33 51 47 34
Françoise Coussen is a CNRS research director. She was trained as a biochemist in the Lab of Ariane Moneron at the Pasteur Institute. During her post-doc in Al Gilman's lab in Dallas, Texas, she cloned for the first time the Adenylate Cyclase , she then worked on the acetylcholinesterase in the lab of Jean Massoulier at the Ecole Normale Supèrieur in Paris. in 1996, she joined the group of Christophe Mulle in Bordeaux and participated to the creation of the Laboratory Physiologie Cellulaire de la Synapse. In 2010, she joined the team of Daniel Choquet and participated to the creation of the Interdisciplinary Institute for Neuroscience and launched a new research area on the intracellular trafficking of AMPA Receptors.
Scientific Context
This activity currently involves Valeria Pecoraro (Post-doctoral fellow), Caroline Bonnet (PhD student) and Justine Charpentier (assistant engineer). 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:
- The characterization of auxiliary proteins in different AMPAR states and localizations.
- The study of post-translational mechanisms involved in the trafficking and physiology of the receptor.
- The improvement of live imaging techniques in order to visualized intracellular transport of AMPAR.
- The regulation of intracellular transport in synaptic plasticity.
Technical approaches
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.
Former Members
Deborah Huyghe (PhD student and post-doctoral fellow) - Cédric Renancio (PhD student) - Amandine Philippat (assistant engineer) - Emilie Hangen (Post-Doc) - Azra Zamri (PhD student)
Selected Publications
Hangen, E., Cordelières, F.P., Petersen, J., Choquet, D. and Coussen, F. 2018. Cell Reports, 24, 1001-1012.
Modulation of AMPA receptor surface diffusion restores hippocampal plasticity and memory in Huntington's disease models.
Zhang, H., Zhang, C., Vincent, J., Zala, D., Benstaali, C., Sainlos, M., Grillo-Bosch, D., Daburon, S., Coussen, F., Cho, Y., David, D.J., Saudou, F., Humeau, Y., and Choquet, D. 2018. Nature Commun, 9(1), 4272-4288.
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)
CaMKII metaplasticity drives Aβ oligomers-mediated synaptotoxicity.
Opazo, P., Viana da Silva, S., Carta, Breillat, C., M., Coultrap, S.J., Grillo-Bosch, D., Sainlos, M., Coussen, F., Bayer, K.U., Mulle, C. and Choquet, D. 2018. Cell Reports, 24, 1001-1012. 23, 3137-3145.
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.
Fundings
This activity is currently funded by the ANR Blanche "PAINT " 2015-2019: F. Coussen (Coord). AMPA receptor transport and the ERC (2019-2020) grant DynnSynMem to Daniel Choquet