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Membrane Traffic at Synapses

Team Leader : David Perrais

David Perrais biosketch

The team (July 2020)

From left to right (without masks): Julie, Lou, Etienne,

David, Silvia, Vincent, May, Zehra, Mathias

 

General objective

Vesicular trafficking is one of the most salient features of synaptic physiology. In the tiny (less than 1 µm wide) chemical synapses, presynaptic vesicles concentrate and release neurotransmitter molecules which bind to post-synaptic receptors. The exocytosis and recycling of synaptic vesicles is a very prominent and essential feature of neuronal physiology that is highly controlled in time and space. Moreover, post-synaptic membrane trafficking, although not as prominent quantitatively, is pivotal for the maintenance of signal transduction complexes supporting synaptic transmission and plasticity. Most of our knowledge about synapse physiology comes from studying glutamatergic synapses which represent the majority of synapses in the brain. Nevertheless, other types of synapses, such as neuromodulatory dopaminergic synapses, could have a very different molecular composition and operate in a different way. However, because they represent a small minority of synapses formed from a very small number of neurons, their analysis has been difficult through classical cellular and molecular methods.

Our goal in the team is to use the most advanced fluorescence imaging techniques together with refined purification of synaptic elements (synaptosomes) to address the mechanisms regulating synapse function through membrane trafficking events in normal brain physiology or in the course of disease. To achieve this goal, we use, on top of the standard techniques of the modern neuroscience lab (molecular biology, biochemistry, imaging, electrophysiology), two unique expertise developed by the two PIs: first, with David Perrais, we develop methods to detect individual exocytosis and endocytosis events with pH sensitive fluorophores and perform quantitative imaging. Second, with Etienne Herzog, we purify synaptosomes from adult animals with fluorescence activated synaptosome sorting (FASS), which enables powerful proteomics, transcriptomics and functional approaches.

Altogether, we aim at identifying new pathways in specific synapses and test their relevance for synaptic nanostructure and function in the normal and diseased brain.

Research Projects

Local Regulation of receptor trafficking in dendrites

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Molecular and cellular mechanisms of endocytosis

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Synaptomic dissection of Dopaminergic projections

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Synaptic alterations and therapeutic approaches in neurodegenerative diseases

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Expertise

  • Imaging endocytosis with the ppH protocol
  • Ex-vivo cellular and molecular analysis of synapses
  • Semi-quantitative imaging of synaptic vesicle super-pool
  • News

    MemTraS: A new team at IINS

    "MemTraS - Membrane traffic at synapses" is a new team recently born at IINS. The leader, David Perrais, presents the research axis:
    Our goal in the team is to study the mechanisms of synapse function. We focus on membrane trafficking events, exocytosis and endocytosis, in normal brain physiology or in the course of disease. Indeed, membrane trafficking is essential in both sides of the synapse. The presynaptic element is filled with synaptic vesicles which fuse at the active zone to release neurotransmitter molecules, one of the defining features of synaptic transmission. After fusion, vesicles are very quickly and efficiently recycled to cope with neuronal activity. At the post-synaptic side, post-synaptic receptors are going through cycles of endocytosis and recycling, which is essential to regulate synaptic transmission and plasticity. We want to analyse how these processes are organized in space and time. 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 researchers 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 in living cells, while Etienne brings his method of purification of synaptosomes from adult animals with fluorescence activated synaptosome sorting 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.

    The members of the team being formed in January 2020 are Lou Bouit, Silvia Sposini, Marlene Pfeffer, Etienne Herzog, May Bakr and David Perrais.

    - More details on the Bordeaux Neurocampus website here.
    - Contact: David Perrais

    MemTraS Team crew is expanding

    We are pleased to welcome several new members:

    Sarka Jelinkova - Post Doctoral Fellow - Expert in Stem cell biology and molecular biology - Ph.D U Brno - Czech Republic

    Nathan Hoareau - Master 2 rotation student - Ecole Supérieure de Chimie Organique et Minerale

    Juan Manuel Defauce Garcia - Master 1 NeuroBIM rotation student - Université de Bordeaux

    Khadija Inam - Master 1 NeuroBIM rotation student - Université de Bordeaux

    Fantine Morinière - Technician degree rotation student - BTS Biotechnologies - Lycée Saint-Louis - Bordeaux

    Welcome to all of them!

    Selected Publications

  • Silvia Sposini, Morgane Rosendale, Léa Claverie, TN Ngoc Van, Damien Jullié & David Perrais
  • Imaging endocytic vesicle formation at high spatial and temporal resolutions with the pulsed-pH protocol Nature Protocols (2020)
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  • Morgane Rosendale, TN Ngoc Van, Dolors Grillo-Bosch, Silvia Sposini, Léa Claverie, Isabel Gautereau, Stéphane Claverol, Daniel Choquet, Matthieu Sainlos & David Perrais
  • Functional recruitment of dynamin requires multimeric interactions for efficient endocytosis Nature Communications (2019)
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  • Hafner A-S, Donlin-Asp PG, Leitch B, Herzog E & Schuman EM.
  • Local protein synthesis is a ubiquitous feature of neuronal pre- and postsynaptic compartments. Science (2019)
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  • Blumenstock S, angelo MF, Peters F, Dorostkar MM, Ruf VC, Luckner M, Crux S, Slapakova L, Arzberger T, Claverol S, Herzog E* & Herms J*
  • Early defects in translation elongation factor 1α levels at excitatory synapses in α-synucleinopathy Acta Neuropathologica (2019)
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  • Zhang XM, Francois U, Silm K, angelo MF, Fernández Busch MV, Maged M, Martin C, Cordelières FP, Deshors M, Pons S, Maskos U, Bemelmans A-P, Wojcik SM, Mestikawy El S, Humeau Y & Herzog E
  • A proline-rich motif on VGLUT1 reduces synaptic vesicle super-pool and spontaneous release frequency eLife (2019)
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  • Magalie Martineau, Agila Somasundaram, Jonathan B Grimm, Todd D Gruber, Daniel Choquet, Justin W Taraska, Luke D Lavis & David Perrais
  • Semisynthetic fluorescent pH sensors for imaging exocytosis and endocytosis Nature Communications (2017)
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  • Morgane Rosendale, Damien Jullié, Daniel Choquet & David Perrais
  • Spatial and temporal regulation of receptor endocytosis in neuronal dendrites revealed by imaging of single vesicle formation Cell Reports (2017)
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    Members

    « Researcher »

    HERZOG Etienne Researcher etienne.herzog@u-bordeaux.fr +33533514861
    PERRAIS David Researcher david.perrais@u-bordeaux.fr +33533514861

    « Technical Staff »

    ANGIBAUD Julie Technical staff julie.angibaud@u-bordeaux.fr +33533514748
    BOUIT Lou Technical staff lou.bouit.1@u-bordeaux.fr +33533514861

    « Postdoc »

    JELINKOVA Sarka Postdoc sarka.jelinkova@u-bordeaux.fr +33533514861
    PAGET-BLANC Vincent Postdoc vincent.paget-blanc@u-bordeaux.fr +33533514861
    SPOSINI Silvia Postdoc silvia.sposini@u-bordeaux.fr +33533514861

    « PhD student »

    LAPIOS Paul PhD student paul.lapios@u-bordeaux.fr +33533514779

    « Student »

    DAFAUCE GARCIA Juan Manuel Student juan-manuel.dafauce-garcia@etu.u-bordeaux.fr +33533514700
    HOAREAU Nathan Student nathan.hoareau@u-bordeaux.fr +33533514700
    INAM Khadija Student khadija.inam@etu.u-bordeaux.fr +33533514700

    « Alumni & Guests »

    Anne-Sophie Hafner (Guest, 2017-2018)

    Magalie Martineau (post-doc, 2015-2019 - Now  Research and Development specialist at EIF Innovation, Paris, France)

    Léa Claverie (PhD student, 2015-2019 - Now Project Manager at Euroquality, Bordeaux, France)

    Florencia Angelo (Lab Manager, 2015-2020)

    Thi Nhu Ngoc Van (post-doc, 2014-2016 - Now Project Manager at Sys2dia, Montpellier, France)

    Julia Krapivkina (PhD student, 2012-2016 - Now Project Manager at Assystem, Paris, France)

    Xiao Min Zhang (PhD Student, 2012-2016 - Now Assistant Prof at Sun Yat Sen University - China)

    Morgane Rosendale (PhD student and post-doc, 2011-2016 - Now post-doctoral fellow at Institute for Molecular Sciences, Bordeaux)

    Damien Jullié (PhD student, 2008-2012 - Now Research Specialist at UCSF Weill Institute for Neurosciences, San Francisco, USA)

    Fundings

    ANR LocalEndoProbes
    ANR-PRC 2019 DopamineHub
    CoEN Pathfinder IV 2019 - LocalDementia