Identification of the SNARE proteins involved in the postsynaptic membrane trafficking
Defended on 29 November 2016
Julia Krapivkina / Membrane Trafficking Lab (PhD student, joint ENC fellowship with Camin Dean, Göttingen) at IINS
Membrane trafficking is a universal process that is essential for neuronal function in a wide spectrum of applications. From neuronal growth and morphological development to neurotransmitter release and synaptic plasticity, it supports neuronal activity and gives countless questions that drive today’s neurobiology research.
Notably, the trafficking of recycling endosomes (REs) in somatodendritic compartments participates in synaptic transmission and plasticity, such as long-term synaptic potentiation (LTP). However, the fusion machinery mediating RE exocytosis is still unclear. To identify the vesicular SNAREs (v-SNAREs) involved in different forms of postsynaptic RE exocytosis, we first imaged neuronal VAMP proteins fused with pH-sensitive pHluorin in cultured hippocampal neurons, and found that only VAMP2 and VAMP4, but not VAMP7, underwent somatodendritic exocytosis in mature neurons.
After identifying these two candidate proteins, we used a combination of different downregulation techniques to chronically or acutely deactivate their function and observe consequences on REs exocytosis, basal synaptic transmission and LTP.
Our results suggest that VAMP2 is involved in activity-regulated exocytosis important for LTP, but not constitutive postsynaptic AMPARs exocytosis, supporting basal transmission. VAMP4 is required for constitutive exocytosis of at least a large proportion of REs, but the functional implication of these endosomes still need to be explored, as VAMP4 downregulation did not alter basal synaptic transmission.
Julia Krapivkina, Damien Jullié, Jennifer Petersen, Natacha Retailleau, Daniel Choquet & David Perrais. The identity if vSNAREs involved in recycling endosomes exocytosis in neuronal dendrites (in preparation).
- GARRET Maurice
Université de Bordeaux – Président du Jury
- DESNOS Claire
Université Paris Descartes – Rapporteur
- El Far Oussama,
Université Aix Marseille – Rapporteur
- DANGLOT Lydia,
Université Paris Diderot – Examinateur
- LANG Jochen,
Université de Bordeaux – Examinateur
- PERRAIS David,
Université de Bordeaux – Directeur de thèse
Directeur de thèse
The Membrane Trafficking axis is integrated into the Dynamics of Synapse Organization and Function group . This activity is headed by David Perrais (DR, senior researcher)