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Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2018
Renseignements relatifs à l’Unité de Recherche :
Label et intitulé : Centre de Psychiatrie et neurosciences INSERM U894
Nom et prénom du Directeur : Thierry GALLI
Téléphone : 01 40 78 92 26 Télécopie : 01 40 78 92 04
courriel : [email protected]
Renseignements relatifs à l’Equipe :
Nom de l’Equipe d’Accueil : Membrane trafic in Heathy & Diseased Brain
Nom et prénom du responsable : GALLI Thierry
Qualité du responsable : DR1 Inserm
Téléphone : 01 40 78 92 26
Télécopie : 01 40 78 92 04
courriel : [email protected]
Renseignements relatifs au sujet de thèse :
Nom et prénom du Directeur de thèse (HDR) : LYDIA DANGLOT
Qualité : Chercheur Inserm, HDR
Téléphone :
06 72 69 38 07
Télécopie : 01 57 27 80 36
Courriel : [email protected]
Titre du sujet proposé : Rôle du trafic vésiculaire dans la synaptogenèse et la plasticité synaptique.
(En français)
(En anglais) Role of vesicular trafficking in synaptogenesis and plasticity.
Département (cocher le département correspondant au sujet de thèse qui n’est pas obligatoirement le
vôtre) :
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
Biologie Cellulaire et moléculaire, Physiologie et Physiopathologie
Immunologie
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Développement Génétique Neurobiologie et Vieillissement
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Infectiologie, Microbiologie
Summary (5 lines maximum) :
The vertebrate central nervous system (CNS) contains billions of neurons, which communicate with each
other through synapses, highly specialized intercellular junctions. Synaptic molecules reach the synapse
via vesicular carriers which merge with the synaptic plasma membrane via SNARE-mediated membrane
fusion. Here we propose a multi-scale project to identify the specificity of vesicular transport
mediated by two main neuronal SNAREs (VAMP2 and VAMP7), in the dynamics of pre and postsynaptic molecules during synaptogenesis and plasticity and ageing.
Proposition de sujet de thèse à l’appui d’une demande de contrat doctoral 2017-2087
Nom, prénom du directeur de l'unité de recherche : GALLI Thierry
Numéro de l'unité de recherche (et établissement de rattachement) : CNRS UMR7592- INSERM950
Nom, prénom du responsable de l'équipe d'accueil (EAD) : GALLI Thierry
Nom, prénom du directeur de thèse : DANGLOT Lydia
Titre du sujet de thèse proposé : Role of vesicular trafficking in synaptogenesis and plasticity
Citer 5 mots clés (key words): Synapse, vesicular transport, plasticity, memory, spine
Candidat pressenti :

OUI

NON
Contenu scientifique du programme de la thèse (en anglais)
The vertebrate central nervous system (CNS) contains billions of neurons, which communicate
with each other at synapses, highly specialized intercellular junctions. Synaptic molecules reach the
synapse via vesicular carriers which merge with the synaptic plasma membrane via SNARE-mediated
membrane fusion and exocytosis. Supposedly, exocytosis, endocytosis and degradation of
molecules are basic mechanisms which support arrival and removal of synaptic proteins, thus
play a role in development, support learning and memory to keep proper structure and function
of synapses, while they may be less efficient in the aging brain.
Two main secretory vesicular SNAREs have been described at synapses:
synaptobrevin2/VAMP2 and TI-VAMP/VAMP7. A large amount of data is available on the role of VAMP2
in neurotransmitter release at presynaptic compartments and on the function of VAMP7 in secretion and
autophagy in non-neuronal cells. However the role of exocytosis in postsynaptic compartments remains
elusive and poorly characterized at the molecular level. Indeed VAMP2 and VAMP7 are also expressed
in the somato-dendritic compartment, a place of intense vesicular trafficking, but there is little data on
their postsynaptic function. Here we propose a multi-scale project to characterize the mechanism and
function of vesicular transport mediated VAMP7 in the dynamics of post-synaptic molecules
during synaptogenesis, plasticity and aging, in a comparative study with VAMP2.
Our preliminary data suggest that VAMP7 KO have improved memory and altered post-synaptic
receptor trafficking. These original data set the grounds for the present project. Our final goal is to now
obtain detailed characterization of the traffic of post-synaptic in cultured neurons following VAMP2 and
VAMP7 inactivation (using live imaging and super-resolution microscopy in WT vs KO, or inhibition by
intrabodies), and in the mouse (WT vs VAMP7 KO) so as to put cognitive (spatial and object recognition
memory), electrophysiological (recordings of Long Term Plasticity), anatomical and molecular data (PSD
composition and single molecule imaging) together with cell biological data. We plan to further study the
role of VAMP7 in neurons aging in vitro and brains of aging mice, which we have already generated.
Altogether, this thesis should allow to decipher the neuronal function of VAMP7 in synapse
formation and maintenance during development and aging.
Indiquez les cinq meilleures publications récentes de l’équipe :
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VAMP7 regulates constitutive membrane incorporation of the cold-activated channel TRPM8.
Ghosh D, Pinto S, Danglot L, Vandewauw I, Segal A, Van Ranst N, Benoit M, Janssens A, Vennekens R, Vanden
Berghe P, Galli T, Vriens J, Voets T.
Nat Commun. (2016) Feb 4;7:10489. doi: 10.1038/ncomms10489.
Role of tetanus neurotoxin insensitive vesicle-associated membrane protein in membrane domains transport and
homeostasis. Molino D, Nola S, Lam SM, Verraes A, Proux-Gillardeaux V, Boncompain G, Perez F, Wenk M, Shui G,
Danglot L*, Galli T*.
* co-senior authors
Cell Logist. (2015) Apr 29;5(1):e1025182. eCollection 2015 Jan-Mar.
The SNARE Sec22b has a non-fusogenic function in plasma membrane expansion. Petkovic M, Jemaiel A, Daste F,
Specht CG, Izeddin I, Vorkel D, Verbavatz JM, Darzacq X, Triller A, Pfenninger KH, Tareste D, Jackson CL, Galli T.
Nature Cell Biology, (2014), 16(5):434-44.
Vezatin is essential for dendritic spine morphogenesis and functional synaptic maturation.
L. Danglot, T. Freret, N. Le Roux, N. Narboux-Nème , A. Burgo, V. Hyenne, A. Roumier, V. Contremoulins, F.
Dauphin, JC Bizot , G. Vodjdani , P. Gaspar, M. Boulouard, JC. Poncer, T. Galli , MC. Simmler.
Journal of Neuroscience (2012), 32 (26):9077-22.
Absence of TI-VAMP/Vamp7 leads to increased anxiety in mice.
L. Danglot*, K. Zylbersztejn*, M. petkovic*, M. Gauberti, H. Meziane, R. Combe, MFChampy, MC Birling, G. Pavlovic,
JC Bizot, F. Trovero, F. della Ragione, V. Proux-Gillardeaux, T. Sorg, D. Vivien, M. D’esposito, and T. Galli.
Journal of Neuroscience (2012), 32 (15): 5186-99. *equal contributions.