||We aim to understand the mechanisms of formation of neuronal synapses and vesicular trafficking allowing transport of synaptic proteins during maintenance and plasticity of excitatory and inhibitory synapses. To do so, we use classical biochemistry, and molecular and cellular biology technics. We also use multi-scales imaging: at the level of the organism with MRI, at the tissular level with confocal tile imaging, and at the cellular and molecular levels with rapid video-microscopy like spinning disc, single particle tracking with QDOTS, and super-resolution microscopy (SIM, STED and STORM).
Formation of synapses in hippocampal neurons.
The hippocampus is a telencephalic structure in the limbic lobe implicated in memory processes and in certain form of pharmaco-resistant epilepsy. The neuronal cells comunicate together by the way of specialized contacts: the synapses, where synaptic vesicles fusion with the plasma membrane to deliver the neurotransmitters in front of the postsynaptic receptors.
During development, hippocampal neurons extend processes that will become axon and dendrites. After 3 weeks in culture in vitro neuronal network is established thanks to synaptic contact (blue ring) betwen the presynaptic axon (here in red) and the somato-dendritic compartment of the post-synaptic neurone (black).
The hippocampal neurons are a good choice to investigate the molecular mechanisms regulating the distribution of synapses, and the distribution of the proteins present in emitting neuron (pre-synaptic compartment) and the receptor neuron (post-synaptic neuron). Wa are focusing on the mechanism leading to apropriate targeting and recycling of proteins at the synaptic contact. We have previously characterized several episode of assembly within different type of synapses.
- Formation of GABAergic inhibitory synapses
Molecular & Cellular Neurosciences (2003), 23:264-278. In Brief Download pdf.
- Discovery of a novel source of inhibition in hippocampus: the glycinergic transmission.
Molecular & Cellular Neurosciences (2004), 27(4):394-403. In brief Download pdf.
- The development of inhibitory interneurons and establishment of GABAergic synapses in vivo.
Hippocampus (2006) 16:1032-1060 (2006). Review. Download pdf.
- Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.
J Neurosci. (2012a), DOI 10.1523/JNEUROSCI.3084-11.2012. Download pdf
- Absence of TI-VAMP/Vamp7 leads to increased anxiety in mice.
J Neurosci. (2012b) Feb 8;32(6):1962-8.
Résumé Pubmed - Download pdf
More recently we focused on the trafic of membranous molecules and vesicular trafficking. Membrane fusion between a vesicle and a target compartment is achieved by SNARE proteins (Soluble N-ethylmaleimide sensitive fusion protein (NSF) Attachment protein Receptor). SNAREs are classifed in 2 types : the v-SNAREs on the vesicles (v- for vesicles) and the t-SNAREs on the target compartment (t- for target). The v-SNAREs and t-SNAREs form complexes which bring closer the two membranes and favors the fusion. We are working on the role of SNARE proteins in the traffic of adhesion molecules and receptors both at the synapse in neuronal cells and in epithelial cells. We have worked on membrane traffic in different physiological contexts:
- Role of SNAREs in neurite outgrowth during developement.
Molecular Biology of the Cell (2006),17(3):1194-203. Download pdf.
- Role of SNAREs in hippocampal synaptic transmission.
PNAS (2006)103 :16562-16567. Download pdf.
- Role of SNAREs in the dynamic of the adhesion molecule L1 at the growth cone.
Molecular Biology of the Cell (2007), 18 : 3131-3143. Download pdf.
- role of Hrb protein in the recylcing and endocytosis of the v-SNARE TI-VAMP.
Journal of Biological Chemistry (2008), 10.1074/jbc.M804587200. Download pdf.
- Transport of the carbohydrate Lewis X in hippocampal neurons.
Brain Research (2009), 1287:39-46, doi:10.1016. Download pdf
- Role of TI-VAMP and CD82 in EGF receptor cell surface dynamics and signaling
Journal of Cell Science (2010), 123:723-735. Download pdf
- VAMP7 controls T cell activation by regulating the recruitment and phosphorylation of vesicular Lat at TCR-activation sites.
Nature Immunology. (2013) May 12. doi: 10.1038/ni.2609. Download pdf
- VAMP-7 links granule exocytosis to actin reorganization during platelet activation.
Blood. (2015) Jul 30;126(5):651-60. doi: 10.1182/blood-2014-12-618744. Download pdf
- Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and homeostasis.
Cell Logist. (2015) Apr 29;5(1):e1025182. eCollection 2015 Jan-Mar.
Pubmed Abstract - Download pdf
- VAMP7 regulates constitutive membrane incorporation of the cold-activated channel TRPM8.
Nat Commun. (2016) Feb 4;7:10489. doi: 10.1038/ncomms10489.
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