Axonal homeostasis of VGLUT1 synaptic vesicles in mice
Defended on December 14, 2016
Soutenance le Mercredi 14/12/16. Xiaomin ZHANG Ph.D student / Interdisciplinary Institute for NeuroScience, Bordeaux / Max Planck Institute of Experimental Medicine, Göttingen.
Team – Synapse in Cognition . Location : CGFB conference room , 14h30 / team Yann Humeau
Synaptic vesicles (SVs) are essential for neurotransmission, and more efforts are needed to better understand their neurotransmitter content, release kinetics, distribution and mobility. SVs are not only clustered in the presynaptic boutons, but also dynamically shared among multiple en passant presynaptic boutons, a phenomenon named SV super-pool. Previous work from our laboratory suggested that Vesicular GLUtamate Transporter 1 (VGLUT1) may play a role in regulating SV super-pool size beyond loading glutamate into SV. My Ph.D project is focused on SVs mobility in axons. Firstly, I generated a VGLUT1mEos2 knock-in (KI) mouse line, which provides extended possibilities to study SV trafficking and characterize SV super-pool. Secondly, I engaged in a thorough VGLUT1 structure-function analysis. I identified that VGLUT1 tends to cluster SVs in the presynaptic boutons and reduce SVs exchange with the super-pool via the second poly-proline motif of its C-terminus. Overall, my Ph.D work contributes to the knowledge of the role of VGLUT1 in regulating SVs mobility and provides new tools for the further investigations on SV super-pool physiology.
Keywords : synaptic vesicle mobility, VGLUT1, super-pool, live imaging, structure-function analyses.
Publications: Zhang XM*., Silm K*., Angelo MF., Peyrot C., Fernandez-busch V., Maged M., Martin C., Cordelière F., Pons S., Maskos U., Bemelmans A., Wojcik SM., Mestikawy S EI, Humeau Y., Brose N., Herzog E,VGLUT1 poly-proline domain controls synaptic vesicle super-pool size in mammals, * equal contribution, in preparation
Zhang X.M., Lipstein N., Angelo M.F., Buttler C., Peyrot C., Martin C., Cordelière F., Sibarita J.B., Humeau Y., Brose N., and Herzog E., Characterization of a VGLUT1mEOS2 knock in mouse line for the study synaptic vesicle mobility in excitatory neurons, in preparation.
Jury
SANS Nathalie
DR-INSERM Bordeaux
Président
OHEIM Martin
DR-CNRS Paris
Rapporteur
MARTY Serge
CR1-CNRS Paris
Rapporteur
DANGLOT Lydia
CR1-INSERM Paris
Examinateur
PERRAIS David
DR-CNRS
Bordeaux
Examinateur
HERZOG Etienne
CR1-CNRS
Bordeaux
Directeur de thèse
Directeur de thèse
Etienne Herzog
Team : Synapse in Cognition
Institut interdisciplinaire de Neurosciences
CNRS UMR 5297
Université de Bordeaux