Membrane traffic at synapses (MemTraS)
Our goal in the team is to study the mechanisms regulating synapse function, focusing on membrane trafficking events in normal brain physiology or in the course of disease. We are interested mainly in the presynaptic element filled with synaptic vesicles fusing to release neurotransmitter molecules as well as the post-synaptic side where post-synaptic receptors are going through cycles of endocytosis and recycling, which is essential for synaptic transmission and plasticity. Finally, we are not only interested in canonical synapses, such as cortical glutamatergic synapses, but also in rare and much less understood synapse populations such as neuromodulatory dopamine synapses. To tackle these issues, we combine two types of expertise mastered by the two PIs of the team, myself and Etienne Herzog. I bring electrophysiology combined with the most advanced fluorescence imaging techniques to detect and characterize individual exocytosis and endocytosis events with pH sensitive fluorophores, while Etienne brings his method of purification of synaptosomes from adult animals with fluorescence activated synaptosome sorting (FASS) which enables powerful proteomics, transcriptomics and functional approaches. Altogether we aim at identifying new principles of organization in specific synapses and test their relevance for synaptic function in the normal and diseased brain.
Mots clésAlzheimer, Analyses des données, Bio-senseurs, Complexes moléculaires de la synapse, Imagerie cellulaire in vitro ou in vivo, Microfluidique, Microscopie super-résolutive, Optogénétique et chemogénétique, Parkinson, Physiologie synaptique, Trafic intracellulaire
Sposini, S., Rosendale, M., Claverie, L., Van, T.N.N., Jullié, D., and Perrais, D. (in press). Imaging endocytic vesicle formation at high spatial and temporal resolutions with the pulsed-pH protocol. Nature Protocols
Hafner, A.-S., Donlin-Asp, P.G., Leitch, B., Herzog, E., and Schuman, E.M. (2019). Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments. Science 364, eaau3644.
Rosendale, M., Van, T.N.N., Grillo-Bosch, D., Sposini, S., Claverie, L., Gauthereau, I., Claverol, S., Choquet, D., Sainlos, M., and Perrais, D. (2019). Functional recruitment of dynamin requires multimeric interactions for efficient endocytosis. Nature Communications 10, 4462.
Zhang, X.M., François, U., Silm, K., Angelo, M.F., Fernandez-Busch, M.V., Maged, M., Martin, C., Bernard, V., Cordelières, F.P., Deshors, M., Pons, S., Maskos, U., Bemelmans, A.P., Wojcik, S.M., El Mestikawy, S., Humeau, Y., and Herzog, E. (2019). A proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency. ELife 8, e50401.
Martineau, M., Somasundaram, A., Grimm, J.B., Gruber, T.D., Choquet, D., Taraska, J.W., Lavis, L.D., and Perrais, D. (2017). Semisynthetic fluorescent pH sensors for imaging exocytosis and endocytosis. Nature Communications 8, 1412.
Rosendale, M., Jullié, D., Choquet, D., and Perrais, D. (2017). Spatial and Temporal Regulation of Receptor Endocytosis in Neuronal Dendrites Revealed by Imaging of Single Vesicle Formation. Cell Reports 18, 1840–1847.
David Perrais Perrais (Team leader)
Chercheurs, Praticiens hospitaliers...